JP7244124B2 - 生体高分子薬を送達するための組成物及び方法 - Google Patents
生体高分子薬を送達するための組成物及び方法 Download PDFInfo
- Publication number
- JP7244124B2 JP7244124B2 JP2021131737A JP2021131737A JP7244124B2 JP 7244124 B2 JP7244124 B2 JP 7244124B2 JP 2021131737 A JP2021131737 A JP 2021131737A JP 2021131737 A JP2021131737 A JP 2021131737A JP 7244124 B2 JP7244124 B2 JP 7244124B2
- Authority
- JP
- Japan
- Prior art keywords
- shdl
- nanoparticles
- cells
- cpg
- antigen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims description 122
- 238000000034 method Methods 0.000 title description 126
- 239000003814 drug Substances 0.000 title description 46
- 229940079593 drug Drugs 0.000 title description 26
- 229920001222 biopolymer Polymers 0.000 title description 19
- 239000002105 nanoparticle Substances 0.000 claims description 292
- 108091007433 antigens Proteins 0.000 claims description 202
- 102000036639 antigens Human genes 0.000 claims description 202
- 239000000427 antigen Substances 0.000 claims description 201
- 239000002671 adjuvant Substances 0.000 claims description 95
- 108020004459 Small interfering RNA Proteins 0.000 claims description 75
- -1 polyIC Proteins 0.000 claims description 53
- 102000007592 Apolipoproteins Human genes 0.000 claims description 46
- 108010071619 Apolipoproteins Proteins 0.000 claims description 46
- 150000003904 phospholipids Chemical class 0.000 claims description 44
- 150000007523 nucleic acids Chemical class 0.000 claims description 30
- 102000039446 nucleic acids Human genes 0.000 claims description 29
- 108020004707 nucleic acids Proteins 0.000 claims description 29
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 claims description 17
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 14
- RHJVIGLEIFVHIJ-UHFFFAOYSA-N cyclohexanecarboxamide Chemical compound NC(=O)C1[CH]CCCC1 RHJVIGLEIFVHIJ-UHFFFAOYSA-N 0.000 claims description 14
- 229960002751 imiquimod Drugs 0.000 claims description 14
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 claims description 14
- 108091034117 Oligonucleotide Proteins 0.000 claims description 12
- 239000012648 POLY-ICLC Substances 0.000 claims description 12
- 229940115270 poly iclc Drugs 0.000 claims description 12
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 11
- 108700002563 poly ICLC Proteins 0.000 claims description 11
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 9
- 230000003308 immunostimulating effect Effects 0.000 claims description 9
- 229950010550 resiquimod Drugs 0.000 claims description 9
- BXNMTOQRYBFHNZ-UHFFFAOYSA-N resiquimod Chemical compound C1=CC=CC2=C(N(C(COCC)=N3)CC(C)(C)O)C3=C(N)N=C21 BXNMTOQRYBFHNZ-UHFFFAOYSA-N 0.000 claims description 9
- GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 claims description 6
- CITHEXJVPOWHKC-UUWRZZSWSA-N 1,2-di-O-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC CITHEXJVPOWHKC-UUWRZZSWSA-N 0.000 claims description 3
- SQQXRXKYTKFFSM-UHFFFAOYSA-N chembl1992147 Chemical compound OC1=C(OC)C(OC)=CC=C1C1=C(C)C(C(O)=O)=NC(C=2N=C3C4=NC(C)(C)N=C4C(OC)=C(O)C3=CC=2)=C1N SQQXRXKYTKFFSM-UHFFFAOYSA-N 0.000 claims 1
- 229940124669 imidazoquinoline Drugs 0.000 claims 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 236
- 206010028980 Neoplasm Diseases 0.000 description 161
- 102000004196 processed proteins & peptides Human genes 0.000 description 161
- 210000004027 cell Anatomy 0.000 description 129
- CTMZLDSMFCVUNX-VMIOUTBZSA-N cytidylyl-(3'->5')-guanosine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@H](OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=C(C(N=C(N)N3)=O)N=C2)O)[C@@H](CO)O1 CTMZLDSMFCVUNX-VMIOUTBZSA-N 0.000 description 80
- 108090000623 proteins and genes Proteins 0.000 description 74
- 108010010234 HDL Lipoproteins Proteins 0.000 description 57
- 102000015779 HDL Lipoproteins Human genes 0.000 description 57
- 102000004169 proteins and genes Human genes 0.000 description 54
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical group C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 53
- 235000018102 proteins Nutrition 0.000 description 53
- 229920001184 polypeptide Polymers 0.000 description 51
- 108010059886 Apolipoprotein A-I Proteins 0.000 description 49
- 102000005666 Apolipoprotein A-I Human genes 0.000 description 49
- 229960005486 vaccine Drugs 0.000 description 49
- 210000001744 T-lymphocyte Anatomy 0.000 description 47
- 230000028993 immune response Effects 0.000 description 46
- 210000004443 dendritic cell Anatomy 0.000 description 42
- 230000035772 mutation Effects 0.000 description 40
- 125000003729 nucleotide group Chemical group 0.000 description 40
- 239000002773 nucleotide Substances 0.000 description 39
- 108020004414 DNA Proteins 0.000 description 38
- 150000002632 lipids Chemical class 0.000 description 35
- 238000012384 transportation and delivery Methods 0.000 description 35
- 235000001014 amino acid Nutrition 0.000 description 34
- 238000009472 formulation Methods 0.000 description 34
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 32
- 201000011510 cancer Diseases 0.000 description 31
- 150000001413 amino acids Chemical class 0.000 description 29
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 27
- 208000035269 cancer or benign tumor Diseases 0.000 description 27
- 235000012000 cholesterol Nutrition 0.000 description 26
- 239000002107 nanodisc Substances 0.000 description 26
- 230000000295 complement effect Effects 0.000 description 24
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 24
- 230000014509 gene expression Effects 0.000 description 24
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 24
- 239000011859 microparticle Substances 0.000 description 24
- 239000002245 particle Substances 0.000 description 24
- 229930186217 Glycolipid Natural products 0.000 description 23
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 22
- 230000001580 bacterial effect Effects 0.000 description 22
- 201000010099 disease Diseases 0.000 description 22
- 239000002041 carbon nanotube Substances 0.000 description 21
- 229910021393 carbon nanotube Inorganic materials 0.000 description 21
- 150000004767 nitrides Chemical class 0.000 description 21
- 102000040430 polynucleotide Human genes 0.000 description 21
- 108091033319 polynucleotide Proteins 0.000 description 21
- 239000002157 polynucleotide Substances 0.000 description 21
- 210000001519 tissue Anatomy 0.000 description 21
- 239000004005 microsphere Substances 0.000 description 20
- 239000002077 nanosphere Substances 0.000 description 20
- 230000001225 therapeutic effect Effects 0.000 description 20
- 238000002474 experimental method Methods 0.000 description 19
- 238000004519 manufacturing process Methods 0.000 description 19
- 238000002255 vaccination Methods 0.000 description 19
- 108010028554 LDL Cholesterol Proteins 0.000 description 18
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 18
- 230000004044 response Effects 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 18
- 230000027455 binding Effects 0.000 description 17
- 238000001727 in vivo Methods 0.000 description 17
- 238000006467 substitution reaction Methods 0.000 description 17
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 17
- 230000003612 virological effect Effects 0.000 description 17
- 108010087614 Apolipoprotein A-II Proteins 0.000 description 16
- 102000009081 Apolipoprotein A-II Human genes 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
- 238000000338 in vitro Methods 0.000 description 16
- 210000000581 natural killer T-cell Anatomy 0.000 description 16
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- 230000008685 targeting Effects 0.000 description 16
- 229940124597 therapeutic agent Drugs 0.000 description 16
- 102100037320 Apolipoprotein A-IV Human genes 0.000 description 15
- 239000013566 allergen Substances 0.000 description 15
- 108010073614 apolipoprotein A-IV Proteins 0.000 description 15
- 239000013604 expression vector Substances 0.000 description 15
- 230000002401 inhibitory effect Effects 0.000 description 15
- 239000000693 micelle Substances 0.000 description 15
- 239000013598 vector Substances 0.000 description 15
- DRHZYJAUECRAJM-DWSYSWFDSA-N (2s,3s,4s,5r,6r)-6-[[(3s,4s,4ar,6ar,6bs,8r,8ar,12as,14ar,14br)-8a-[(2s,3r,4s,5r,6r)-3-[(2s,3r,4s,5r,6s)-5-[(2s,3r,4s,5r)-4-[(2s,3r,4r)-3,4-dihydroxy-4-(hydroxymethyl)oxolan-2-yl]oxy-3,5-dihydroxyoxan-2-yl]oxy-3,4-dihydroxy-6-methyloxan-2-yl]oxy-5-[(3s,5s, Chemical compound O([C@H]1[C@H](O)[C@H](O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O1)O)O[C@H]1CC[C@]2(C)[C@H]3CC=C4[C@@H]5CC(C)(C)CC[C@@]5([C@@H](C[C@@]4(C)[C@]3(C)CC[C@H]2[C@@]1(C=O)C)O)C(=O)O[C@@H]1O[C@H](C)[C@@H]([C@@H]([C@H]1O[C@H]1[C@@H]([C@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@](O)(CO)CO3)O)[C@H](O)CO2)O)[C@H](C)O1)O)O)OC(=O)C[C@@H](O)C[C@H](OC(=O)C[C@@H](O)C[C@@H]([C@@H](C)CC)O[C@H]1[C@@H]([C@@H](O)[C@H](CO)O1)O)[C@@H](C)CC)C(O)=O)[C@@H]1OC[C@@H](O)[C@H](O)[C@H]1O DRHZYJAUECRAJM-DWSYSWFDSA-N 0.000 description 14
- 241001465754 Metazoa Species 0.000 description 14
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 14
- 102000002689 Toll-like receptor Human genes 0.000 description 14
- 108020000411 Toll-like receptor Proteins 0.000 description 14
- 230000009368 gene silencing by RNA Effects 0.000 description 14
- 229910052737 gold Inorganic materials 0.000 description 14
- 239000010931 gold Substances 0.000 description 14
- 239000012216 imaging agent Substances 0.000 description 14
- JVJGCCBAOOWGEO-RUTPOYCXSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-4-amino-2-[[(2s,3s)-2-[[(2s,3s)-2-[[(2s)-2-azaniumyl-3-hydroxypropanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-phenylpropanoyl]amino]-4-carboxylatobutanoyl]amino]-6-azaniumy Chemical compound OC[C@H](N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(O)=O)CC1=CC=CC=C1 JVJGCCBAOOWGEO-RUTPOYCXSA-N 0.000 description 13
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 13
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 13
- 241000700605 Viruses Species 0.000 description 13
- 125000003275 alpha amino acid group Chemical group 0.000 description 13
- 210000000612 antigen-presenting cell Anatomy 0.000 description 13
- 229910052796 boron Inorganic materials 0.000 description 13
- 238000009566 cancer vaccine Methods 0.000 description 13
- 229940022399 cancer vaccine Drugs 0.000 description 13
- 102000037865 fusion proteins Human genes 0.000 description 13
- 108020001507 fusion proteins Proteins 0.000 description 13
- 230000001404 mediated effect Effects 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- 241000894006 Bacteria Species 0.000 description 12
- XMWRBQBLMFGWIX-UHFFFAOYSA-N C60 fullerene Chemical class C12=C3C(C4=C56)=C7C8=C5C5=C9C%10=C6C6=C4C1=C1C4=C6C6=C%10C%10=C9C9=C%11C5=C8C5=C8C7=C3C3=C7C2=C1C1=C2C4=C6C4=C%10C6=C9C9=C%11C5=C5C8=C3C3=C7C1=C1C2=C4C6=C2C9=C5C3=C12 XMWRBQBLMFGWIX-UHFFFAOYSA-N 0.000 description 12
- 102000000853 LDL receptors Human genes 0.000 description 12
- 108010001831 LDL receptors Proteins 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 101150094724 PCSK9 gene Proteins 0.000 description 12
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 12
- 230000000890 antigenic effect Effects 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 12
- 238000002296 dynamic light scattering Methods 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 229910003472 fullerene Inorganic materials 0.000 description 12
- 238000005227 gel permeation chromatography Methods 0.000 description 12
- 230000006698 induction Effects 0.000 description 12
- 239000008194 pharmaceutical composition Substances 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 238000012163 sequencing technique Methods 0.000 description 12
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 11
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 11
- 102100022430 Melanocyte protein PMEL Human genes 0.000 description 11
- 230000005867 T cell response Effects 0.000 description 11
- 229960004784 allergens Drugs 0.000 description 11
- 239000001913 cellulose Substances 0.000 description 11
- 229920002678 cellulose Polymers 0.000 description 11
- 239000002299 complementary DNA Substances 0.000 description 11
- 239000000412 dendrimer Substances 0.000 description 11
- 229920000736 dendritic polymer Polymers 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 11
- 238000002347 injection Methods 0.000 description 11
- 239000007924 injection Substances 0.000 description 11
- 229910052742 iron Inorganic materials 0.000 description 11
- 239000002502 liposome Substances 0.000 description 11
- 239000002073 nanorod Substances 0.000 description 11
- 239000002071 nanotube Substances 0.000 description 11
- 239000002096 quantum dot Substances 0.000 description 11
- 210000002966 serum Anatomy 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 102100029470 Apolipoprotein E Human genes 0.000 description 10
- 101710095339 Apolipoprotein E Proteins 0.000 description 10
- 238000011740 C57BL/6 mouse Methods 0.000 description 10
- FOIXSVOLVBLSDH-UHFFFAOYSA-N Silver ion Chemical compound [Ag+] FOIXSVOLVBLSDH-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- 238000005516 engineering process Methods 0.000 description 10
- 239000011521 glass Substances 0.000 description 10
- 210000003494 hepatocyte Anatomy 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- 230000001939 inductive effect Effects 0.000 description 10
- 239000012678 infectious agent Substances 0.000 description 10
- 239000003446 ligand Substances 0.000 description 10
- 108020004999 messenger RNA Proteins 0.000 description 10
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 10
- 239000002048 multi walled nanotube Substances 0.000 description 10
- 239000002116 nanohorn Substances 0.000 description 10
- 239000002078 nanoshell Substances 0.000 description 10
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 10
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 10
- 239000002109 single walled nanotube Substances 0.000 description 10
- 241000701806 Human papillomavirus Species 0.000 description 9
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 9
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 9
- 108091008874 T cell receptors Proteins 0.000 description 9
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 description 9
- 238000013459 approach Methods 0.000 description 9
- 239000011852 carbon nanoparticle Substances 0.000 description 9
- 230000003834 intracellular effect Effects 0.000 description 9
- 230000021633 leukocyte mediated immunity Effects 0.000 description 9
- 201000001441 melanoma Diseases 0.000 description 9
- 230000001613 neoplastic effect Effects 0.000 description 9
- 244000045947 parasite Species 0.000 description 9
- XGOYIMQSIKSOBS-UHFFFAOYSA-N vadimezan Chemical compound C1=CC=C2C(=O)C3=CC=C(C)C(C)=C3OC2=C1CC(O)=O XGOYIMQSIKSOBS-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 241000272478 Aquila Species 0.000 description 8
- 102000004127 Cytokines Human genes 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 8
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 8
- 108091081021 Sense strand Proteins 0.000 description 8
- 230000004913 activation Effects 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 230000021615 conjugation Effects 0.000 description 8
- 208000029078 coronary artery disease Diseases 0.000 description 8
- 238000001514 detection method Methods 0.000 description 8
- 238000004108 freeze drying Methods 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 210000001165 lymph node Anatomy 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 239000002609 medium Substances 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 230000000069 prophylactic effect Effects 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 230000028327 secretion Effects 0.000 description 8
- 230000000638 stimulation Effects 0.000 description 8
- 238000007920 subcutaneous administration Methods 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 210000004881 tumor cell Anatomy 0.000 description 8
- FYGDTMLNYKFZSV-URKRLVJHSA-N (2s,3r,4s,5s,6r)-2-[(2r,4r,5r,6s)-4,5-dihydroxy-2-(hydroxymethyl)-6-[(2r,4r,5r,6s)-4,5,6-trihydroxy-2-(hydroxymethyl)oxan-3-yl]oxyoxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1[C@@H](CO)O[C@@H](OC2[C@H](O[C@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-URKRLVJHSA-N 0.000 description 7
- 229920002498 Beta-glucan Polymers 0.000 description 7
- DJSXIWXIOUHBRL-ICBMVRCQSA-N CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)SC(C)O)OC(=O)CCCCCCCCCCCCCCC Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)SC(C)O)OC(=O)CCCCCCCCCCCCCCC DJSXIWXIOUHBRL-ICBMVRCQSA-N 0.000 description 7
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 7
- 241000282412 Homo Species 0.000 description 7
- 102000004895 Lipoproteins Human genes 0.000 description 7
- 108090001030 Lipoproteins Proteins 0.000 description 7
- 108091054437 MHC class I family Proteins 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- GUVMFDICMFQHSZ-UHFFFAOYSA-N N-(1-aminoethenyl)-1-[4-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[5-(4-amino-5-methyl-2-oxopyrimidin-1-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[hydroxy-[[3-[hydroxy-[[3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy]phosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(2-amino-6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxyoxolan-2-yl]methoxy-hydroxyphosphinothioyl]oxy-5-[[[2-[[[2-[[[5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[5-(4-amino-2-oxopyrimidin-1-yl)-2-[[hydroxy-[2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphinothioyl]oxymethyl]oxolan-2-yl]-5-methylimidazole-4-carboxamide Chemical compound CC1=C(C(=O)NC(N)=C)N=CN1C1OC(COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)CO)C(OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(N=C(N)C=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)OP(O)(=S)OCC2C(CC(O2)N2C(NC(=O)C(C)=C2)=O)O)C1 GUVMFDICMFQHSZ-UHFFFAOYSA-N 0.000 description 7
- 108010084333 N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine Proteins 0.000 description 7
- 108010060818 Toll-Like Receptor 9 Proteins 0.000 description 7
- 102100033117 Toll-like receptor 9 Human genes 0.000 description 7
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 7
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 7
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 7
- 230000030741 antigen processing and presentation Effects 0.000 description 7
- 239000002246 antineoplastic agent Substances 0.000 description 7
- 230000001413 cellular effect Effects 0.000 description 7
- 108010017271 denileukin diftitox Proteins 0.000 description 7
- 229940056913 eftilagimod alfa Drugs 0.000 description 7
- 230000002209 hydrophobic effect Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 238000011068 loading method Methods 0.000 description 7
- 229940035032 monophosphoryl lipid a Drugs 0.000 description 7
- 229940100027 ontak Drugs 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 244000052769 pathogen Species 0.000 description 7
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 7
- 150000003905 phosphatidylinositols Chemical class 0.000 description 7
- 230000003389 potentiating effect Effects 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 229950008737 vadimezan Drugs 0.000 description 7
- 239000000277 virosome Substances 0.000 description 7
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical class CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 102000015735 Beta-catenin Human genes 0.000 description 6
- 108060000903 Beta-catenin Proteins 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 101710204837 Envelope small membrane protein Proteins 0.000 description 6
- 101710113436 GTPase KRas Proteins 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 6
- 108091028043 Nucleic acid sequence Proteins 0.000 description 6
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 6
- 101710088839 Replication initiation protein Proteins 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 229940127089 cytotoxic agent Drugs 0.000 description 6
- 238000009826 distribution Methods 0.000 description 6
- 238000000684 flow cytometry Methods 0.000 description 6
- 150000004676 glycans Chemical class 0.000 description 6
- 210000000987 immune system Anatomy 0.000 description 6
- 230000001976 improved effect Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 229920001282 polysaccharide Polymers 0.000 description 6
- 239000005017 polysaccharide Substances 0.000 description 6
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 6
- 239000000829 suppository Substances 0.000 description 6
- 238000004627 transmission electron microscopy Methods 0.000 description 6
- 230000032258 transport Effects 0.000 description 6
- VQFKFAKEUMHBLV-BYSUZVQFSA-N 1-O-(alpha-D-galactosyl)-N-hexacosanoylphytosphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)[C@H](O)CCCCCCCCCCCCCC)CO[C@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQFKFAKEUMHBLV-BYSUZVQFSA-N 0.000 description 5
- HVCOBJNICQPDBP-UHFFFAOYSA-N 3-[3-[3,5-dihydroxy-6-methyl-4-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid;hydrate Chemical compound O.OC1C(OC(CC(=O)OC(CCCCCCC)CC(O)=O)CCCCCCC)OC(C)C(O)C1OC1C(O)C(O)C(O)C(C)O1 HVCOBJNICQPDBP-UHFFFAOYSA-N 0.000 description 5
- 102000018619 Apolipoproteins A Human genes 0.000 description 5
- 108010027004 Apolipoproteins A Proteins 0.000 description 5
- 108091026890 Coding region Proteins 0.000 description 5
- 238000001712 DNA sequencing Methods 0.000 description 5
- 208000001490 Dengue Diseases 0.000 description 5
- 206010012310 Dengue fever Diseases 0.000 description 5
- 108060002716 Exonuclease Proteins 0.000 description 5
- 241000238631 Hexapoda Species 0.000 description 5
- 206010020751 Hypersensitivity Diseases 0.000 description 5
- 102000043129 MHC class I family Human genes 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 229930012538 Paclitaxel Natural products 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 210000003719 b-lymphocyte Anatomy 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000012472 biological sample Substances 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 208000025729 dengue disease Diseases 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 102000013165 exonuclease Human genes 0.000 description 5
- 239000012634 fragment Substances 0.000 description 5
- 238000003197 gene knockdown Methods 0.000 description 5
- 230000003053 immunization Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 238000003780 insertion Methods 0.000 description 5
- 230000037431 insertion Effects 0.000 description 5
- 208000032839 leukemia Diseases 0.000 description 5
- 230000004048 modification Effects 0.000 description 5
- 238000012986 modification Methods 0.000 description 5
- 229960001592 paclitaxel Drugs 0.000 description 5
- 239000013573 pollen allergen Substances 0.000 description 5
- 238000010149 post-hoc-test Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000012552 review Methods 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 238000001542 size-exclusion chromatography Methods 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 230000004083 survival effect Effects 0.000 description 5
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 5
- 230000004614 tumor growth Effects 0.000 description 5
- 238000007492 two-way ANOVA Methods 0.000 description 5
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 4
- 201000001320 Atherosclerosis Diseases 0.000 description 4
- 210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 241000701044 Human gammaherpesvirus 4 Species 0.000 description 4
- 102000018697 Membrane Proteins Human genes 0.000 description 4
- 108010052285 Membrane Proteins Proteins 0.000 description 4
- RWKUXQNLWDTSLO-GWQJGLRPSA-N N-hexadecanoylsphingosine-1-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)[C@H](O)\C=C\CCCCCCCCCCCCC RWKUXQNLWDTSLO-GWQJGLRPSA-N 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- 102000014190 Phosphatidylcholine-sterol O-acyltransferase Human genes 0.000 description 4
- 108010011964 Phosphatidylcholine-sterol O-acyltransferase Proteins 0.000 description 4
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 4
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 4
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 4
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 241000256856 Vespidae Species 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 210000005006 adaptive immune system Anatomy 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 230000004071 biological effect Effects 0.000 description 4
- 210000004556 brain Anatomy 0.000 description 4
- 150000001720 carbohydrates Chemical class 0.000 description 4
- 210000002421 cell wall Anatomy 0.000 description 4
- 230000037430 deletion Effects 0.000 description 4
- 238000012217 deletion Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000002158 endotoxin Substances 0.000 description 4
- 230000007613 environmental effect Effects 0.000 description 4
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 4
- 239000007850 fluorescent dye Substances 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 229920000669 heparin Polymers 0.000 description 4
- 238000003384 imaging method Methods 0.000 description 4
- 230000036039 immunity Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000001506 immunosuppresive effect Effects 0.000 description 4
- 238000009169 immunotherapy Methods 0.000 description 4
- 238000010348 incorporation Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 210000005007 innate immune system Anatomy 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 229920006008 lipopolysaccharide Polymers 0.000 description 4
- 239000003550 marker Substances 0.000 description 4
- 230000035800 maturation Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 229910021645 metal ion Inorganic materials 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 229960005489 paracetamol Drugs 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 238000010647 peptide synthesis reaction Methods 0.000 description 4
- 230000002093 peripheral effect Effects 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 102000054765 polymorphisms of proteins Human genes 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000000734 protein sequencing Methods 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- 229910052709 silver Inorganic materials 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 230000004936 stimulating effect Effects 0.000 description 4
- 230000002459 sustained effect Effects 0.000 description 4
- 230000002194 synthesizing effect Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 238000013518 transcription Methods 0.000 description 4
- 230000002103 transcriptional effect Effects 0.000 description 4
- 230000007704 transition Effects 0.000 description 4
- 150000003626 triacylglycerols Chemical class 0.000 description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
- LKKMLIBUAXYLOY-UHFFFAOYSA-N 3-Amino-1-methyl-5H-pyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1C=C(N)N=C2C LKKMLIBUAXYLOY-UHFFFAOYSA-N 0.000 description 3
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 3
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 3
- 102100030310 5,6-dihydroxyindole-2-carboxylic acid oxidase Human genes 0.000 description 3
- 101710163881 5,6-dihydroxyindole-2-carboxylic acid oxidase Proteins 0.000 description 3
- 101710163573 5-hydroxyisourate hydrolase Proteins 0.000 description 3
- 102100030840 AT-rich interactive domain-containing protein 4B Human genes 0.000 description 3
- 108700028369 Alleles Proteins 0.000 description 3
- 102100032959 Alpha-actinin-4 Human genes 0.000 description 3
- 101710115256 Alpha-actinin-4 Proteins 0.000 description 3
- 102100035526 B melanoma antigen 1 Human genes 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 229940045513 CTLA4 antagonist Drugs 0.000 description 3
- 101100005789 Caenorhabditis elegans cdk-4 gene Proteins 0.000 description 3
- 102100026548 Caspase-8 Human genes 0.000 description 3
- 102100035167 Coiled-coil domain-containing protein 54 Human genes 0.000 description 3
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 description 3
- 102000013701 Cyclin-Dependent Kinase 4 Human genes 0.000 description 3
- 108010072210 Cyclophilin C Proteins 0.000 description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 101100216227 Dictyostelium discoideum anapc3 gene Proteins 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 108010066687 Epithelial Cell Adhesion Molecule Proteins 0.000 description 3
- 102000018651 Epithelial Cell Adhesion Molecule Human genes 0.000 description 3
- 108010008165 Etanercept Proteins 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 102100028073 Fibroblast growth factor 5 Human genes 0.000 description 3
- 108090000380 Fibroblast growth factor 5 Proteins 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- 102100039717 G antigen 1 Human genes 0.000 description 3
- 102100039788 GTPase NRas Human genes 0.000 description 3
- 102100040510 Galectin-3-binding protein Human genes 0.000 description 3
- 101710197901 Galectin-3-binding protein Proteins 0.000 description 3
- 102100041003 Glutamate carboxypeptidase 2 Human genes 0.000 description 3
- 108010036972 HLA-A11 Antigen Proteins 0.000 description 3
- 108010074032 HLA-A2 Antigen Proteins 0.000 description 3
- 102000025850 HLA-A2 Antigen Human genes 0.000 description 3
- 241000711549 Hepacivirus C Species 0.000 description 3
- 101000792935 Homo sapiens AT-rich interactive domain-containing protein 4B Proteins 0.000 description 3
- 101000874316 Homo sapiens B melanoma antigen 1 Proteins 0.000 description 3
- 101000737052 Homo sapiens Coiled-coil domain-containing protein 54 Proteins 0.000 description 3
- 101000866749 Homo sapiens Elongation factor 2 Proteins 0.000 description 3
- 101000886137 Homo sapiens G antigen 1 Proteins 0.000 description 3
- 101000744505 Homo sapiens GTPase NRas Proteins 0.000 description 3
- 101000892862 Homo sapiens Glutamate carboxypeptidase 2 Proteins 0.000 description 3
- 101000934372 Homo sapiens Macrosialin Proteins 0.000 description 3
- 101000620359 Homo sapiens Melanocyte protein PMEL Proteins 0.000 description 3
- 101001036406 Homo sapiens Melanoma-associated antigen C1 Proteins 0.000 description 3
- 101000610208 Homo sapiens Poly(A) polymerase gamma Proteins 0.000 description 3
- 101001136592 Homo sapiens Prostate stem cell antigen Proteins 0.000 description 3
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
- 101001062222 Homo sapiens Receptor-binding cancer antigen expressed on SiSo cells Proteins 0.000 description 3
- 101000591201 Homo sapiens Receptor-type tyrosine-protein phosphatase kappa Proteins 0.000 description 3
- 101001073409 Homo sapiens Retrotransposon-derived protein PEG10 Proteins 0.000 description 3
- 101000973629 Homo sapiens Ribosome quality control complex subunit NEMF Proteins 0.000 description 3
- 101000824971 Homo sapiens Sperm surface protein Sp17 Proteins 0.000 description 3
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 3
- 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 3
- 101000671653 Homo sapiens U3 small nucleolar RNA-associated protein 14 homolog A Proteins 0.000 description 3
- 108010052919 Hydroxyethylthiazole kinase Proteins 0.000 description 3
- 108010027436 Hydroxymethylpyrimidine kinase Proteins 0.000 description 3
- 206010062016 Immunosuppression Diseases 0.000 description 3
- 108010030506 Integrin alpha6beta4 Proteins 0.000 description 3
- 108010014726 Interferon Type I Proteins 0.000 description 3
- 102000002227 Interferon Type I Human genes 0.000 description 3
- 102100037850 Interferon gamma Human genes 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 108010050904 Interferons Proteins 0.000 description 3
- 102000014150 Interferons Human genes 0.000 description 3
- 102100031413 L-dopachrome tautomerase Human genes 0.000 description 3
- 101710093778 L-dopachrome tautomerase Proteins 0.000 description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
- 108010007622 LDL Lipoproteins Proteins 0.000 description 3
- 102000007330 LDL Lipoproteins Human genes 0.000 description 3
- 102000016200 MART-1 Antigen Human genes 0.000 description 3
- 108010010995 MART-1 Antigen Proteins 0.000 description 3
- 102100025136 Macrosialin Human genes 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 102100039447 Melanoma-associated antigen C1 Human genes 0.000 description 3
- 102000003505 Myosin Human genes 0.000 description 3
- 108060008487 Myosin Chemical class 0.000 description 3
- 108060006580 PRAME Proteins 0.000 description 3
- 102000036673 PRAME Human genes 0.000 description 3
- 102100024968 Peptidyl-prolyl cis-trans isomerase C Human genes 0.000 description 3
- 102100040153 Poly(A) polymerase gamma Human genes 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- 108010080283 Pre-beta High-Density Lipoproteins Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102100036735 Prostate stem cell antigen Human genes 0.000 description 3
- 108010026552 Proteome Proteins 0.000 description 3
- 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
- 102100029165 Receptor-binding cancer antigen expressed on SiSo cells Human genes 0.000 description 3
- 102100034089 Receptor-type tyrosine-protein phosphatase kappa Human genes 0.000 description 3
- 102100035844 Retrotransposon-derived protein PEG10 Human genes 0.000 description 3
- 102100022213 Ribosome quality control complex subunit NEMF Human genes 0.000 description 3
- 101710173693 Short transient receptor potential channel 1 Proteins 0.000 description 3
- 101710173694 Short transient receptor potential channel 2 Proteins 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 101710143177 Synaptonemal complex protein 1 Proteins 0.000 description 3
- 102100036234 Synaptonemal complex protein 1 Human genes 0.000 description 3
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 3
- 101150031162 TM4SF1 gene Proteins 0.000 description 3
- 108010017842 Telomerase Proteins 0.000 description 3
- 102100024324 Toll-like receptor 3 Human genes 0.000 description 3
- 102100034902 Transmembrane 4 L6 family member 1 Human genes 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 102000005924 Triose-Phosphate Isomerase Human genes 0.000 description 3
- 108700015934 Triose-phosphate isomerases Proteins 0.000 description 3
- LVTKHGUGBGNBPL-UHFFFAOYSA-N Trp-P-1 Chemical compound N1C2=CC=CC=C2C2=C1C(C)=C(N)N=C2C LVTKHGUGBGNBPL-UHFFFAOYSA-N 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 102000003425 Tyrosinase Human genes 0.000 description 3
- 108060008724 Tyrosinase Proteins 0.000 description 3
- 102100040099 U3 small nucleolar RNA-associated protein 14 homolog A Human genes 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 229960002964 adalimumab Drugs 0.000 description 3
- 102000013529 alpha-Fetoproteins Human genes 0.000 description 3
- 108010026331 alpha-Fetoproteins Proteins 0.000 description 3
- 230000003321 amplification Effects 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000014102 antigen processing and presentation of exogenous peptide antigen via MHC class I Effects 0.000 description 3
- 230000002238 attenuated effect Effects 0.000 description 3
- 108010056708 bcr-abl Fusion Proteins Proteins 0.000 description 3
- 102000004441 bcr-abl Fusion Proteins Human genes 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 238000004422 calculation algorithm Methods 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000036755 cellular response Effects 0.000 description 3
- 238000010367 cloning Methods 0.000 description 3
- 239000000562 conjugate Substances 0.000 description 3
- 239000002872 contrast media Substances 0.000 description 3
- 229960004397 cyclophosphamide Drugs 0.000 description 3
- 210000000172 cytosol Anatomy 0.000 description 3
- 238000011033 desalting Methods 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 239000000975 dye Substances 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- 239000012636 effector Substances 0.000 description 3
- 229960000403 etanercept Drugs 0.000 description 3
- 239000012091 fetal bovine serum Substances 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 238000013467 fragmentation Methods 0.000 description 3
- 238000006062 fragmentation reaction Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 210000003128 head Anatomy 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 230000028996 humoral immune response Effects 0.000 description 3
- 229920001600 hydrophobic polymer Polymers 0.000 description 3
- 239000002955 immunomodulating agent Substances 0.000 description 3
- 229940121354 immunomodulator Drugs 0.000 description 3
- 239000003018 immunosuppressive agent Substances 0.000 description 3
- 229960000598 infliximab Drugs 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 229940079322 interferon Drugs 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- 230000002132 lysosomal effect Effects 0.000 description 3
- 210000003712 lysosome Anatomy 0.000 description 3
- 230000001868 lysosomic effect Effects 0.000 description 3
- 210000002540 macrophage Anatomy 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 238000007726 management method Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229960000485 methotrexate Drugs 0.000 description 3
- PUPNJSIFIXXJCH-UHFFFAOYSA-N n-(4-hydroxyphenyl)-2-(1,1,3-trioxo-1,2-benzothiazol-2-yl)acetamide Chemical compound C1=CC(O)=CC=C1NC(=O)CN1S(=O)(=O)C2=CC=CC=C2C1=O PUPNJSIFIXXJCH-UHFFFAOYSA-N 0.000 description 3
- AEMBWNDIEFEPTH-UHFFFAOYSA-N n-tert-butyl-n-ethylnitrous amide Chemical compound CCN(N=O)C(C)(C)C AEMBWNDIEFEPTH-UHFFFAOYSA-N 0.000 description 3
- 238000003199 nucleic acid amplification method Methods 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 229920001481 poly(stearyl methacrylate) Polymers 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 238000003259 recombinant expression Methods 0.000 description 3
- 210000003289 regulatory T cell Anatomy 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 229960004641 rituximab Drugs 0.000 description 3
- 150000003839 salts Chemical group 0.000 description 3
- 230000003248 secreting effect Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000007790 solid phase Substances 0.000 description 3
- 230000037436 splice-site mutation Effects 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 101150047061 tag-72 gene Proteins 0.000 description 3
- RCINICONZNJXQF-XAZOAEDWSA-N taxol® Chemical compound O([C@@H]1[C@@]2(CC(C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3(C21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-XAZOAEDWSA-N 0.000 description 3
- MPLHNVLQVRSVEE-UHFFFAOYSA-N texas red Chemical compound [O-]S(=O)(=O)C1=CC(S(Cl)(=O)=O)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 MPLHNVLQVRSVEE-UHFFFAOYSA-N 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 238000013519 translation Methods 0.000 description 3
- 108010020589 trehalose-6-phosphate synthase Proteins 0.000 description 3
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 2
- JWDFQMWEFLOOED-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) 3-(pyridin-2-yldisulfanyl)propanoate Chemical compound O=C1CCC(=O)N1OC(=O)CCSSC1=CC=CC=N1 JWDFQMWEFLOOED-UHFFFAOYSA-N 0.000 description 2
- FELGMEQIXOGIFQ-CYBMUJFWSA-N (3r)-9-methyl-3-[(2-methylimidazol-1-yl)methyl]-2,3-dihydro-1h-carbazol-4-one Chemical compound CC1=NC=CN1C[C@@H]1C(=O)C(C=2C(=CC=CC=2)N2C)=C2CC1 FELGMEQIXOGIFQ-CYBMUJFWSA-N 0.000 description 2
- SLKDGVPOSSLUAI-PGUFJCEWSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCCCC SLKDGVPOSSLUAI-PGUFJCEWSA-N 0.000 description 2
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 description 2
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 description 2
- BIABMEZBCHDPBV-MPQUPPDSSA-N 1,2-palmitoyl-sn-glycero-3-phospho-(1'-sn-glycerol) Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCCCCCCCCCC BIABMEZBCHDPBV-MPQUPPDSSA-N 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 2
- VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 2
- ZXWQZGROTQMXME-WXUJBLQXSA-N 2-hydroxy-n-[(e,2s,3r)-3-hydroxy-1-[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoctadec-4-en-2-yl]tetracosanamide Chemical class CCCCCCCCCCCCCCCCCCCCCCC(O)C(=O)N[C@H]([C@H](O)\C=C\CCCCCCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O ZXWQZGROTQMXME-WXUJBLQXSA-N 0.000 description 2
- HSHNITRMYYLLCV-UHFFFAOYSA-N 4-methylumbelliferone Chemical compound C1=C(O)C=CC2=C1OC(=O)C=C2C HSHNITRMYYLLCV-UHFFFAOYSA-N 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 2
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 2
- LVXACIPXSUHNDE-CTNRBZHLSA-N 98805-74-4 Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(O)C=C1 LVXACIPXSUHNDE-CTNRBZHLSA-N 0.000 description 2
- 102000006410 Apoproteins Human genes 0.000 description 2
- 108010083590 Apoproteins Proteins 0.000 description 2
- 101000719121 Arabidopsis thaliana Protein MEI2-like 1 Proteins 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 0.000 description 2
- 102000005427 Asialoglycoprotein Receptor Human genes 0.000 description 2
- 108010024976 Asparaginase Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 101710201279 Biotin carboxyl carrier protein Proteins 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 2
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 2
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- 241000726768 Carpinus Species 0.000 description 2
- 102000000844 Cell Surface Receptors Human genes 0.000 description 2
- 108010001857 Cell Surface Receptors Proteins 0.000 description 2
- 241000498849 Chlamydiales Species 0.000 description 2
- JWBOIMRXGHLCPP-UHFFFAOYSA-N Chloditan Chemical compound C=1C=CC=C(Cl)C=1C(C(Cl)Cl)C1=CC=C(Cl)C=C1 JWBOIMRXGHLCPP-UHFFFAOYSA-N 0.000 description 2
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 2
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 241000711573 Coronaviridae Species 0.000 description 2
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
- 241000701022 Cytomegalovirus Species 0.000 description 2
- 150000008574 D-amino acids Chemical class 0.000 description 2
- CYQFCXCEBYINGO-DLBZAZTESA-N Dronabinol Natural products C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@H]21 CYQFCXCEBYINGO-DLBZAZTESA-N 0.000 description 2
- 241000709661 Enterovirus Species 0.000 description 2
- 108010074604 Epoetin Alfa Proteins 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- 108010029961 Filgrastim Proteins 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 241000531123 GB virus C Species 0.000 description 2
- GYHNNYVSQQEPJS-UHFFFAOYSA-N Gallium Chemical compound [Ga] GYHNNYVSQQEPJS-UHFFFAOYSA-N 0.000 description 2
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 2
- 241000941423 Grom virus Species 0.000 description 2
- 241000724675 Hepatitis E virus Species 0.000 description 2
- 241000709721 Hepatovirus A Species 0.000 description 2
- 208000009889 Herpes Simplex Diseases 0.000 description 2
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 2
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 2
- 101001082073 Homo sapiens Interferon-induced helicase C domain-containing protein 1 Proteins 0.000 description 2
- 101000857677 Homo sapiens Runt-related transcription factor 1 Proteins 0.000 description 2
- 241000701024 Human betaherpesvirus 5 Species 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- 241000257303 Hymenoptera Species 0.000 description 2
- 108010046315 IDL Lipoproteins Proteins 0.000 description 2
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 2
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 2
- 102100022297 Integrin alpha-X Human genes 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102100027353 Interferon-induced helicase C domain-containing protein 1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108091092195 Intron Proteins 0.000 description 2
- 108090001090 Lectins Proteins 0.000 description 2
- 102000004856 Lectins Human genes 0.000 description 2
- HLFSDGLLUJUHTE-SNVBAGLBSA-N Levamisole Chemical compound C1([C@H]2CN3CCSC3=N2)=CC=CC=C1 HLFSDGLLUJUHTE-SNVBAGLBSA-N 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 102000043131 MHC class II family Human genes 0.000 description 2
- 108091054438 MHC class II family Proteins 0.000 description 2
- 241000712079 Measles morbillivirus Species 0.000 description 2
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 description 2
- 229930192392 Mitomycin Natural products 0.000 description 2
- 241000204031 Mycoplasma Species 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Natural products CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 108700026244 Open Reading Frames Proteins 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 241000209504 Poaceae Species 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 241000606701 Rickettsia Species 0.000 description 2
- 241000702670 Rotavirus Species 0.000 description 2
- 102100025373 Runt-related transcription factor 1 Human genes 0.000 description 2
- 108091005487 SCARB1 Proteins 0.000 description 2
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 2
- 102100037118 Scavenger receptor class B member 1 Human genes 0.000 description 2
- 108020004682 Single-Stranded DNA Proteins 0.000 description 2
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 2
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
- MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000033289 adaptive immune response Effects 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 238000012382 advanced drug delivery Methods 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 108700025316 aldesleukin Proteins 0.000 description 2
- 229960005310 aldesleukin Drugs 0.000 description 2
- 229960000473 altretamine Drugs 0.000 description 2
- JKOQGQFVAUAYPM-UHFFFAOYSA-N amifostine Chemical compound NCCCNCCSP(O)(O)=O JKOQGQFVAUAYPM-UHFFFAOYSA-N 0.000 description 2
- 229960001097 amifostine Drugs 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000005875 antibody response Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 108010006523 asialoglycoprotein receptor Proteins 0.000 description 2
- 229960003272 asparaginase Drugs 0.000 description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 2
- 238000004630 atomic force microscopy Methods 0.000 description 2
- 230000005784 autoimmunity Effects 0.000 description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 229960001561 bleomycin Drugs 0.000 description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 210000000746 body region Anatomy 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 210000000481 breast Anatomy 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229960004117 capecitabine Drugs 0.000 description 2
- 229960004562 carboplatin Drugs 0.000 description 2
- 229960005243 carmustine Drugs 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 2
- 230000020411 cell activation Effects 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229930183167 cerebroside Natural products 0.000 description 2
- 150000001784 cerebrosides Chemical class 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 150000001840 cholesterol esters Chemical class 0.000 description 2
- DCSUBABJRXZOMT-IRLDBZIGSA-N cisapride Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-IRLDBZIGSA-N 0.000 description 2
- 229960005132 cisapride Drugs 0.000 description 2
- DCSUBABJRXZOMT-UHFFFAOYSA-N cisapride Natural products C1CC(NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)C(OC)CN1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-UHFFFAOYSA-N 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 229960002436 cladribine Drugs 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000011260 co-administration Methods 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 2
- 201000010897 colon adenocarcinoma Diseases 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 229960000684 cytarabine Drugs 0.000 description 2
- 229960003901 dacarbazine Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 235000021186 dishes Nutrition 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 229960004242 dronabinol Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 230000012202 endocytosis Effects 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 229960003388 epoetin alfa Drugs 0.000 description 2
- 229960005420 etoposide Drugs 0.000 description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 2
- 210000003527 eukaryotic cell Anatomy 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 229960004177 filgrastim Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 229960000390 fludarabine Drugs 0.000 description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000008191 folinic acid Nutrition 0.000 description 2
- 239000011672 folinic acid Substances 0.000 description 2
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 2
- 230000037433 frameshift Effects 0.000 description 2
- 229910052733 gallium Inorganic materials 0.000 description 2
- 150000002270 gangliosides Chemical class 0.000 description 2
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 229960001743 golimumab Drugs 0.000 description 2
- MFWNKCLOYSRHCJ-BTTYYORXSA-N granisetron Chemical compound C1=CC=C2C(C(=O)N[C@H]3C[C@H]4CCC[C@@H](C3)N4C)=NN(C)C2=C1 MFWNKCLOYSRHCJ-BTTYYORXSA-N 0.000 description 2
- 229960003727 granisetron Drugs 0.000 description 2
- 208000029570 hepatitis D virus infection Diseases 0.000 description 2
- 235000008216 herbs Nutrition 0.000 description 2
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 2
- 230000008348 humoral response Effects 0.000 description 2
- 238000009396 hybridization Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229960000908 idarubicin Drugs 0.000 description 2
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 2
- 229960001101 ifosfamide Drugs 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 230000001900 immune effect Effects 0.000 description 2
- 230000006058 immune tolerance Effects 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 2
- 206010022000 influenza Diseases 0.000 description 2
- 229950000038 interferon alfa Drugs 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 229960005386 ipilimumab Drugs 0.000 description 2
- 229910052741 iridium Inorganic materials 0.000 description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 description 2
- 229960004768 irinotecan Drugs 0.000 description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 229960003174 lansoprazole Drugs 0.000 description 2
- MJIHNNLFOKEZEW-UHFFFAOYSA-N lansoprazole Chemical compound CC1=C(OCC(F)(F)F)C=CN=C1CS(=O)C1=NC2=CC=CC=C2N1 MJIHNNLFOKEZEW-UHFFFAOYSA-N 0.000 description 2
- 239000002523 lectin Substances 0.000 description 2
- 229960001691 leucovorin Drugs 0.000 description 2
- 229960001614 levamisole Drugs 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 210000003563 lymphoid tissue Anatomy 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 230000003211 malignant effect Effects 0.000 description 2
- 210000004962 mammalian cell Anatomy 0.000 description 2
- 229960001786 megestrol Drugs 0.000 description 2
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 2
- 229960004635 mesna Drugs 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 229960004503 metoclopramide Drugs 0.000 description 2
- TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 229960004857 mitomycin Drugs 0.000 description 2
- 229960000350 mitotane Drugs 0.000 description 2
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 2
- 229960001156 mitoxantrone Drugs 0.000 description 2
- 238000009126 molecular therapy Methods 0.000 description 2
- 210000000822 natural killer cell Anatomy 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 229960000381 omeprazole Drugs 0.000 description 2
- 229960005343 ondansetron Drugs 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 230000005298 paramagnetic effect Effects 0.000 description 2
- 102000007863 pattern recognition receptors Human genes 0.000 description 2
- 108010089193 pattern recognition receptors Proteins 0.000 description 2
- 229940023041 peptide vaccine Drugs 0.000 description 2
- 239000000816 peptidomimetic Substances 0.000 description 2
- 210000005259 peripheral blood Anatomy 0.000 description 2
- 239000011886 peripheral blood Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229960001416 pilocarpine Drugs 0.000 description 2
- 229910052697 platinum Inorganic materials 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- WIKYUJGCLQQFNW-UHFFFAOYSA-N prochlorperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 WIKYUJGCLQQFNW-UHFFFAOYSA-N 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 229940021993 prophylactic vaccine Drugs 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 238000001742 protein purification Methods 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 230000004141 reverse cholesterol transport Effects 0.000 description 2
- 210000003296 saliva Anatomy 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000004332 silver Substances 0.000 description 2
- 238000002741 site-directed mutagenesis Methods 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 210000003046 sporozoite Anatomy 0.000 description 2
- 210000000130 stem cell Anatomy 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 229960001603 tamoxifen Drugs 0.000 description 2
- 229910052713 technetium Inorganic materials 0.000 description 2
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 2
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
- 229940021747 therapeutic vaccine Drugs 0.000 description 2
- 210000001541 thymus gland Anatomy 0.000 description 2
- 229940044655 toll-like receptor 9 agonist Drugs 0.000 description 2
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 2
- 229960002190 topotecan hydrochloride Drugs 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- 241000701161 unidentified adenovirus Species 0.000 description 2
- 230000003827 upregulation Effects 0.000 description 2
- 239000012646 vaccine adjuvant Substances 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000002435 venom Substances 0.000 description 2
- 210000001048 venom Anatomy 0.000 description 2
- 231100000611 venom Toxicity 0.000 description 2
- 229960003048 vinblastine Drugs 0.000 description 2
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 2
- 229960004528 vincristine Drugs 0.000 description 2
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 2
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 2
- 229960002166 vinorelbine tartrate Drugs 0.000 description 2
- GBABOYUKABKIAF-IWWDSPBFSA-N vinorelbinetartrate Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC(C23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IWWDSPBFSA-N 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- 238000007482 whole exome sequencing Methods 0.000 description 2
- 238000012070 whole genome sequencing analysis Methods 0.000 description 2
- 229910052727 yttrium Inorganic materials 0.000 description 2
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 description 1
- DMWMUMWKGKGSNW-OPMCLZTFSA-N (2S)-6-amino-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S)-4-amino-2-[[2-[[(2R)-2-amino-3-[(2R)-2,3-di(hexadecanoyloxy)propyl]sulfanylpropanoyl]amino]acetyl]amino]-4-oxobutanoyl]amino]-4-oxobutanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-hydroxypropanoyl]amino]-4-oxobutanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxypropanoyl]amino]-3-phenylpropanoyl]amino]hexanoyl]amino]-4-carboxybutanoyl]amino]hexanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](CSC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(O)=O)OC(=O)CCCCCCCCCCCCCCC DMWMUMWKGKGSNW-OPMCLZTFSA-N 0.000 description 1
- VLPIATFUUWWMKC-SNVBAGLBSA-N (2r)-1-(2,6-dimethylphenoxy)propan-2-amine Chemical compound C[C@@H](N)COC1=C(C)C=CC=C1C VLPIATFUUWWMKC-SNVBAGLBSA-N 0.000 description 1
- YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 1
- WKJDWDLHIOUPPL-JSOSNVBQSA-N (2s)-2-amino-3-({[(2r)-2,3-bis(tetradecanoyloxy)propoxy](hydroxy)phosphoryl}oxy)propanoic acid Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCC WKJDWDLHIOUPPL-JSOSNVBQSA-N 0.000 description 1
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- XUKUURHRXDUEBC-SVBPBHIXSA-N (3s,5s)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SVBPBHIXSA-N 0.000 description 1
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- TVYLLZQTGLZFBW-ZBFHGGJFSA-N (R,R)-tramadol Chemical compound COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-ZBFHGGJFSA-N 0.000 description 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
- FYNNIUVBDKICAX-UHFFFAOYSA-M 1,1',3,3'-tetraethyl-5,5',6,6'-tetrachloroimidacarbocyanine iodide Chemical compound [I-].CCN1C2=CC(Cl)=C(Cl)C=C2N(CC)C1=CC=CC1=[N+](CC)C2=CC(Cl)=C(Cl)C=C2N1CC FYNNIUVBDKICAX-UHFFFAOYSA-M 0.000 description 1
- MWRBNPKJOOWZPW-NYVOMTAGSA-N 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-NYVOMTAGSA-N 0.000 description 1
- NRJAVPSFFCBXDT-HUESYALOSA-N 1,2-distearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCC NRJAVPSFFCBXDT-HUESYALOSA-N 0.000 description 1
- OZSITQMWYBNPMW-GDLZYMKVSA-N 1,2-ditetradecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCC OZSITQMWYBNPMW-GDLZYMKVSA-N 0.000 description 1
- PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
- BPIUIOXAFBGMNB-UHFFFAOYSA-N 1-hexoxyhexane Chemical compound CCCCCCOCCCCCC BPIUIOXAFBGMNB-UHFFFAOYSA-N 0.000 description 1
- RFVFQQWKPSOBED-PSXMRANNSA-N 1-myristoyl-2-palmitoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCC RFVFQQWKPSOBED-PSXMRANNSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- VGIRNWJSIRVFRT-UHFFFAOYSA-N 2',7'-difluorofluorescein Chemical compound OC(=O)C1=CC=CC=C1C1=C2C=C(F)C(=O)C=C2OC2=CC(O)=C(F)C=C21 VGIRNWJSIRVFRT-UHFFFAOYSA-N 0.000 description 1
- PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 1
- IJFVSSZAOYLHEE-UHFFFAOYSA-N 2,3-di(dodecanoyloxy)propyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCC IJFVSSZAOYLHEE-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- IXZONVAEGFOVSF-UHFFFAOYSA-N 2-(5'-chloro-2'-phosphoryloxyphenyl)-6-chloro-4-(3H)-quinazolinone Chemical compound OP(O)(=O)OC1=CC=C(Cl)C=C1C1=NC(=O)C2=CC(Cl)=CC=C2N1 IXZONVAEGFOVSF-UHFFFAOYSA-N 0.000 description 1
- VTAKZNRDSPNOAU-UHFFFAOYSA-M 2-(chloromethyl)oxirane;hydron;prop-2-en-1-amine;n-prop-2-enyldecan-1-amine;trimethyl-[6-(prop-2-enylamino)hexyl]azanium;dichloride Chemical compound Cl.[Cl-].NCC=C.ClCC1CO1.CCCCCCCCCCNCC=C.C[N+](C)(C)CCCCCCNCC=C VTAKZNRDSPNOAU-UHFFFAOYSA-M 0.000 description 1
- RUVJFMSQTCEAAB-UHFFFAOYSA-M 2-[3-[5,6-dichloro-1,3-bis[[4-(chloromethyl)phenyl]methyl]benzimidazol-2-ylidene]prop-1-enyl]-3-methyl-1,3-benzoxazol-3-ium;chloride Chemical compound [Cl-].O1C2=CC=CC=C2[N+](C)=C1C=CC=C(N(C1=CC(Cl)=C(Cl)C=C11)CC=2C=CC(CCl)=CC=2)N1CC1=CC=C(CCl)C=C1 RUVJFMSQTCEAAB-UHFFFAOYSA-M 0.000 description 1
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(O)(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 1
- LRYZPFWEZHSTHD-HEFFAWAOSA-O 2-[[(e,2s,3r)-2-formamido-3-hydroxyoctadec-4-enoxy]-hydroxyphosphoryl]oxyethyl-trimethylazanium Chemical class CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](NC=O)COP(O)(=O)OCC[N+](C)(C)C LRYZPFWEZHSTHD-HEFFAWAOSA-O 0.000 description 1
- IOJUJUOXKXMJNF-UHFFFAOYSA-N 2-acetyloxybenzoic acid [3-(nitrooxymethyl)phenyl] ester Chemical compound CC(=O)OC1=CC=CC=C1C(=O)OC1=CC=CC(CO[N+]([O-])=O)=C1 IOJUJUOXKXMJNF-UHFFFAOYSA-N 0.000 description 1
- NEZDNQCXEZDCBI-UHFFFAOYSA-N 2-azaniumylethyl 2,3-di(tetradecanoyloxy)propyl phosphate Chemical compound CCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCC NEZDNQCXEZDCBI-UHFFFAOYSA-N 0.000 description 1
- JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 description 1
- 108020005345 3' Untranslated Regions Proteins 0.000 description 1
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
- YPGZWUVVEWKKDQ-UHFFFAOYSA-M 4-(4-dihexadecylaminostyryl)-N-methylpyridium iodide Chemical compound [I-].C1=CC(N(CCCCCCCCCCCCCCCC)CCCCCCCCCCCCCCCC)=CC=C1C=CC1=CC=[N+](C)C=C1 YPGZWUVVEWKKDQ-UHFFFAOYSA-M 0.000 description 1
- XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 1
- 108020003589 5' Untranslated Regions Proteins 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- VWOLRKMFAJUZGM-UHFFFAOYSA-N 6-carboxyrhodamine 6G Chemical compound [Cl-].C=12C=C(C)C(NCC)=CC2=[O+]C=2C=C(NCC)C(C)=CC=2C=1C1=CC(C(O)=O)=CC=C1C(=O)OCC VWOLRKMFAJUZGM-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010001513 AIDS related complex Diseases 0.000 description 1
- 102100032814 ATP-dependent zinc metalloprotease YME1L1 Human genes 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 241000186046 Actinomyces Species 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 229920000936 Agarose Polymers 0.000 description 1
- 108010011170 Ala-Trp-Arg-His-Pro-Gln-Phe-Gly-Gly Proteins 0.000 description 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 1
- 239000012099 Alexa Fluor family Substances 0.000 description 1
- 244000291564 Allium cepa Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- 241000219496 Alnus Species 0.000 description 1
- 241000223600 Alternaria Species 0.000 description 1
- 241000192542 Anabaena Species 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 102000008873 Angiotensin II receptor Human genes 0.000 description 1
- 108050000824 Angiotensin II receptor Proteins 0.000 description 1
- 108010058207 Anistreplase Proteins 0.000 description 1
- 102100037435 Antiviral innate immune response receptor RIG-I Human genes 0.000 description 1
- 101710127675 Antiviral innate immune response receptor RIG-I Proteins 0.000 description 1
- 241000710189 Aphthovirus Species 0.000 description 1
- 241000256837 Apidae Species 0.000 description 1
- 101100271206 Arabidopsis thaliana ATHB-15 gene Proteins 0.000 description 1
- 101001007348 Arachis hypogaea Galactose-binding lectin Proteins 0.000 description 1
- 241000712892 Arenaviridae Species 0.000 description 1
- 241001533362 Astroviridae Species 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000003950 B-cell lymphoma Diseases 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
- 102000008096 B7-H1 Antigen Human genes 0.000 description 1
- 108010074708 B7-H1 Antigen Proteins 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 108020000946 Bacterial DNA Proteins 0.000 description 1
- 108020004513 Bacterial RNA Proteins 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 241000701412 Baculoviridae Species 0.000 description 1
- 241001533460 Barnaviridae Species 0.000 description 1
- 241000604933 Bdellovibrio Species 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- 241000219429 Betula Species 0.000 description 1
- 235000003932 Betula Nutrition 0.000 description 1
- 241000702628 Birnaviridae Species 0.000 description 1
- 241000238658 Blattella Species 0.000 description 1
- 241001674044 Blattodea Species 0.000 description 1
- TYBKADJAOBUHAD-UHFFFAOYSA-J BoBo-1 Chemical compound [I-].[I-].[I-].[I-].S1C2=CC=CC=C2[N+](C)=C1C=C1C=CN(CCC[N+](C)(C)CCC[N+](C)(C)CCCN2C=CC(=CC3=[N+](C4=CC=CC=C4S3)C)C=C2)C=C1 TYBKADJAOBUHAD-UHFFFAOYSA-J 0.000 description 1
- 241000588807 Bordetella Species 0.000 description 1
- 241000589968 Borrelia Species 0.000 description 1
- 241000701822 Bovine papillomavirus Species 0.000 description 1
- 241000339490 Brachyachne Species 0.000 description 1
- 241001533462 Bromoviridae Species 0.000 description 1
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 1
- 102100028667 C-type lectin domain family 4 member A Human genes 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 239000002083 C09CA01 - Losartan Substances 0.000 description 1
- 239000002080 C09CA02 - Eprosartan Substances 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000002081 C09CA05 - Tasosartan Substances 0.000 description 1
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 1
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
- 239000002051 C09CA08 - Olmesartan medoxomil Substances 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- 102100032912 CD44 antigen Human genes 0.000 description 1
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 1
- 102100035793 CD83 antigen Human genes 0.000 description 1
- 229940127291 Calcium channel antagonist Drugs 0.000 description 1
- 241000714198 Caliciviridae Species 0.000 description 1
- 102000000584 Calmodulin Human genes 0.000 description 1
- 108010041952 Calmodulin Proteins 0.000 description 1
- 241000589876 Campylobacter Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000222178 Candida tropicalis Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 108010078791 Carrier Proteins Proteins 0.000 description 1
- 241000863012 Caulobacter Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- 241000256128 Chironomus <genus> Species 0.000 description 1
- 241000606161 Chlamydia Species 0.000 description 1
- 241000191366 Chlorobium Species 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 206010008761 Choriomeningitis lymphocytic Diseases 0.000 description 1
- 241000190831 Chromatium Species 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- 108010004942 Chylomicron Remnants Proteins 0.000 description 1
- 108010004103 Chylomicrons Proteins 0.000 description 1
- 241001533399 Circoviridae Species 0.000 description 1
- 241000222290 Cladosporium Species 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 241000973027 Closteroviridae Species 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 108091033380 Coding strand Proteins 0.000 description 1
- 229920002905 Colesevelam Polymers 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 241000701520 Corticoviridae Species 0.000 description 1
- 241000723382 Corylus Species 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 241000709687 Coxsackievirus Species 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 241000699802 Cricetulus griseus Species 0.000 description 1
- 201000007336 Cryptococcosis Diseases 0.000 description 1
- 241000221204 Cryptococcus neoformans Species 0.000 description 1
- 240000005109 Cryptomeria japonica Species 0.000 description 1
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 description 1
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 description 1
- 241000702221 Cystoviridae Species 0.000 description 1
- 241000605056 Cytophaga Species 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 108010037897 DC-specific ICAM-3 grabbing nonintegrin Proteins 0.000 description 1
- YVGGHNCTFXOJCH-UHFFFAOYSA-N DDT Chemical compound C1=CC(Cl)=CC=C1C(C(Cl)(Cl)Cl)C1=CC=C(Cl)C=C1 YVGGHNCTFXOJCH-UHFFFAOYSA-N 0.000 description 1
- VLLFXWZDQHOGLC-UHFFFAOYSA-N DND-167 dye Chemical compound C=12C=CC=CC2=C(CN2CCOCC2)C2=CC=CC=C2C=1CN1CCOCC1 VLLFXWZDQHOGLC-UHFFFAOYSA-N 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 241000209210 Dactylis Species 0.000 description 1
- 241000192093 Deinococcus Species 0.000 description 1
- 241001533413 Deltavirus Species 0.000 description 1
- 241000725619 Dengue virus Species 0.000 description 1
- 241000710827 Dengue virus 1 Species 0.000 description 1
- 241000710815 Dengue virus 2 Species 0.000 description 1
- 241000710872 Dengue virus 3 Species 0.000 description 1
- 241000710844 Dengue virus 4 Species 0.000 description 1
- 241000238710 Dermatophagoides Species 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000723672 Dianthovirus Species 0.000 description 1
- KLFKZIQAIPDJCW-HTIIIDOHSA-N Dipalmitoylphosphatidylserine Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCC KLFKZIQAIPDJCW-HTIIIDOHSA-N 0.000 description 1
- 101100072149 Drosophila melanogaster eIF2alpha gene Proteins 0.000 description 1
- 229910052692 Dysprosium Inorganic materials 0.000 description 1
- 241001115402 Ebolavirus Species 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 241000723747 Enamovirus Species 0.000 description 1
- 206010014596 Encephalitis Japanese B Diseases 0.000 description 1
- 241000224431 Entamoeba Species 0.000 description 1
- 241000991587 Enterovirus C Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108010056764 Eptifibatide Proteins 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000000832 Equine Encephalomyelitis Diseases 0.000 description 1
- 229910052691 Erbium Inorganic materials 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241000238739 Euroglyphus Species 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- 108700024394 Exon Proteins 0.000 description 1
- 206010051841 Exposure to allergen Diseases 0.000 description 1
- VZUVCAGXYLMFEC-UHFFFAOYSA-L FM 1-43 dye Chemical compound [Br-].[Br-].C1=CC(N(CCCC)CCCC)=CC=C1C=CC1=CC=[N+](CCC[N+](CC)(CC)CC)C=C1 VZUVCAGXYLMFEC-UHFFFAOYSA-L 0.000 description 1
- YLCOJTKDARPCKE-UHFFFAOYSA-L FM 4-64 dye Chemical compound [Br-].[Br-].C1=CC(N(CCCC)CCCC)=CC=C1C=CC=CC=CC1=CC=[N+](CCC[N+](CC)(CC)CC)C=C1 YLCOJTKDARPCKE-UHFFFAOYSA-L 0.000 description 1
- 241000219428 Fagaceae Species 0.000 description 1
- 108010087819 Fc receptors Proteins 0.000 description 1
- 102000009109 Fc receptors Human genes 0.000 description 1
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 1
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 241000711950 Filoviridae Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 108010040721 Flagellin Proteins 0.000 description 1
- 241000710781 Flaviviridae Species 0.000 description 1
- DJBNUMBKLMJRSA-UHFFFAOYSA-N Flecainide Chemical compound FC(F)(F)COC1=CC=C(OCC(F)(F)F)C(C(=O)NCC2NCCCC2)=C1 DJBNUMBKLMJRSA-UHFFFAOYSA-N 0.000 description 1
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
- OUVXYXNWSVIOSJ-UHFFFAOYSA-N Fluo-4 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(F)C(=O)C=C3OC3=CC(O)=C(F)C=C32)N(CC(O)=O)CC(O)=O)=C1 OUVXYXNWSVIOSJ-UHFFFAOYSA-N 0.000 description 1
- 241001507629 Formicidae Species 0.000 description 1
- 241000589601 Francisella Species 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241001510533 Glycyphagus Species 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- WDZVGELJXXEGPV-YIXHJXPBSA-N Guanabenz Chemical compound NC(N)=N\N=C\C1=C(Cl)C=CC=C1Cl WDZVGELJXXEGPV-YIXHJXPBSA-N 0.000 description 1
- INJOMKTZOLKMBF-UHFFFAOYSA-N Guanfacine Chemical compound NC(=N)NC(=O)CC1=C(Cl)C=CC=C1Cl INJOMKTZOLKMBF-UHFFFAOYSA-N 0.000 description 1
- HVLSXIKZNLPZJJ-TXZCQADKSA-N HA peptide Chemical compound C([C@@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 HVLSXIKZNLPZJJ-TXZCQADKSA-N 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 102100029966 HLA class II histocompatibility antigen, DP alpha 1 chain Human genes 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 241000606790 Haemophilus Species 0.000 description 1
- 241000205062 Halobacterium Species 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
- 101710154606 Hemagglutinin Proteins 0.000 description 1
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 1
- 241000700739 Hepadnaviridae Species 0.000 description 1
- 241000700721 Hepatitis B virus Species 0.000 description 1
- 208000005331 Hepatitis D Diseases 0.000 description 1
- 241000709715 Hepatovirus Species 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 241000700586 Herpesviridae Species 0.000 description 1
- 241000228404 Histoplasma capsulatum Species 0.000 description 1
- 241000744855 Holcus Species 0.000 description 1
- 229910052689 Holmium Inorganic materials 0.000 description 1
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 1
- 101000766908 Homo sapiens C-type lectin domain family 4 member A Proteins 0.000 description 1
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
- 101000946856 Homo sapiens CD83 antigen Proteins 0.000 description 1
- 101000864089 Homo sapiens HLA class II histocompatibility antigen, DP alpha 1 chain Proteins 0.000 description 1
- 101000930802 Homo sapiens HLA class II histocompatibility antigen, DQ alpha 1 chain Proteins 0.000 description 1
- 101000968032 Homo sapiens HLA class II histocompatibility antigen, DR beta 3 chain Proteins 0.000 description 1
- 101001018097 Homo sapiens L-selectin Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 101100352903 Homo sapiens PPP3CA gene Proteins 0.000 description 1
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 description 1
- 101000643024 Homo sapiens Stimulator of interferon genes protein Proteins 0.000 description 1
- 101000669447 Homo sapiens Toll-like receptor 4 Proteins 0.000 description 1
- 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 1
- 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 1
- 241000701027 Human herpesvirus 6 Species 0.000 description 1
- 241000713340 Human immunodeficiency virus 2 Species 0.000 description 1
- 241000711920 Human orthopneumovirus Species 0.000 description 1
- 208000010152 Huntington disease-like 3 Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 241000862974 Hyphomicrobium Species 0.000 description 1
- 101150103227 IFN gene Proteins 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- ALOBUEHUHMBRLE-UHFFFAOYSA-N Ibutilide Chemical compound CCCCCCCN(CC)CCCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ALOBUEHUHMBRLE-UHFFFAOYSA-N 0.000 description 1
- 206010021450 Immunodeficiency congenital Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241001500351 Influenzavirus A Species 0.000 description 1
- 241001500350 Influenzavirus B Species 0.000 description 1
- 241001500343 Influenzavirus C Species 0.000 description 1
- 108700001097 Insect Genes Proteins 0.000 description 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 241000701377 Iridoviridae Species 0.000 description 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- 201000005807 Japanese encephalitis Diseases 0.000 description 1
- 241000710842 Japanese encephalitis virus Species 0.000 description 1
- 241000721662 Juniperus Species 0.000 description 1
- 101710172072 Kexin Proteins 0.000 description 1
- 102100033467 L-selectin Human genes 0.000 description 1
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 1
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 241000714210 Leviviridae Species 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- 241000186781 Listeria Species 0.000 description 1
- 241000209082 Lolium Species 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 102100033486 Lymphocyte antigen 75 Human genes 0.000 description 1
- 101710157884 Lymphocyte antigen 75 Proteins 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 241000829100 Macaca mulatta polyomavirus 1 Species 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 101710175625 Maltose/maltodextrin-binding periplasmic protein Proteins 0.000 description 1
- 108010031099 Mannose Receptor Proteins 0.000 description 1
- 241001115401 Marburgvirus Species 0.000 description 1
- 101710085938 Matrix protein Proteins 0.000 description 1
- 108091027974 Mature messenger RNA Proteins 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 101710127721 Membrane protein Proteins 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241000202974 Methanobacterium Species 0.000 description 1
- CESYKOGBSMNBPD-UHFFFAOYSA-N Methyclothiazide Chemical compound ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CCl)NC2=C1 CESYKOGBSMNBPD-UHFFFAOYSA-N 0.000 description 1
- 108060004795 Methyltransferase Proteins 0.000 description 1
- 108700005443 Microbial Genes Proteins 0.000 description 1
- 241000192041 Micrococcus Species 0.000 description 1
- 241000702318 Microviridae Species 0.000 description 1
- ZFMITUMMTDLWHR-UHFFFAOYSA-N Minoxidil Chemical compound NC1=[N+]([O-])C(N)=CC(N2CCCCC2)=N1 ZFMITUMMTDLWHR-UHFFFAOYSA-N 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 108010085220 Multiprotein Complexes Proteins 0.000 description 1
- 102000007474 Multiprotein Complexes Human genes 0.000 description 1
- 208000005647 Mumps Diseases 0.000 description 1
- 241000711386 Mumps virus Species 0.000 description 1
- MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 101100412856 Mus musculus Rhod gene Proteins 0.000 description 1
- 241000202934 Mycoplasma pneumoniae Species 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 241000863420 Myxococcus Species 0.000 description 1
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical compound CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical compound CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- SXZWBNWTCVLZJN-NMIJJABPSA-N N-tricosanoylsphing-4-enine-1-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)[C@H](O)\C=C\CCCCCCCCCCCCC SXZWBNWTCVLZJN-NMIJJABPSA-N 0.000 description 1
- 108010057466 NF-kappa B Proteins 0.000 description 1
- 102000003945 NF-kappa B Human genes 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 description 1
- 241000605159 Nitrobacter Species 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 241000187678 Nocardia asteroides Species 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 241000795633 Olea <sea slug> Species 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- UQGKUQLKSCSZGY-UHFFFAOYSA-N Olmesartan medoxomil Chemical compound C=1C=C(C=2C(=CC=CC=2)C2=NNN=N2)C=CC=1CN1C(CCC)=NC(C(C)(C)O)=C1C(=O)OCC=1OC(=O)OC=1C UQGKUQLKSCSZGY-UHFFFAOYSA-N 0.000 description 1
- 241000712464 Orthomyxoviridae Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241000192497 Oscillatoria Species 0.000 description 1
- 101710093908 Outer capsid protein VP4 Proteins 0.000 description 1
- 101710135467 Outer capsid protein sigma-1 Proteins 0.000 description 1
- FVJZSBGHRPJMMA-IOLBBIBUSA-N PG(18:0/18:0) Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCCCCCCCCCCCC FVJZSBGHRPJMMA-IOLBBIBUSA-N 0.000 description 1
- 101150025129 POP1 gene Proteins 0.000 description 1
- 241001631646 Papillomaviridae Species 0.000 description 1
- 241000711504 Paramyxoviridae Species 0.000 description 1
- 208000002606 Paramyxoviridae Infections Diseases 0.000 description 1
- 241000701945 Parvoviridae Species 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010013639 Peptidoglycan Proteins 0.000 description 1
- 241000150350 Peribunyaviridae Species 0.000 description 1
- 241000238661 Periplaneta Species 0.000 description 1
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 241000745991 Phalaris Species 0.000 description 1
- QZVCTJOXCFMACW-UHFFFAOYSA-N Phenoxybenzamine Chemical compound C=1C=CC=CC=1CN(CCCl)C(C)COC1=CC=CC=C1 QZVCTJOXCFMACW-UHFFFAOYSA-N 0.000 description 1
- 241000746981 Phleum Species 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 241000709664 Picornaviridae Species 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 241000224016 Plasmodium Species 0.000 description 1
- 241000223960 Plasmodium falciparum Species 0.000 description 1
- 241000209466 Platanus Species 0.000 description 1
- 241000209048 Poa Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- CYLWJCABXYDINA-UHFFFAOYSA-N Polythiazide Polymers ClC1=C(S(N)(=O)=O)C=C2S(=O)(=O)N(C)C(CSCC(F)(F)F)NC2=C1 CYLWJCABXYDINA-UHFFFAOYSA-N 0.000 description 1
- 241000700625 Poxviridae Species 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 101800000795 Proadrenomedullin N-20 terminal peptide Proteins 0.000 description 1
- 241000192141 Prochloron Species 0.000 description 1
- 108010044159 Proprotein Convertases Proteins 0.000 description 1
- 102000006437 Proprotein Convertases Human genes 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 101710176177 Protein A56 Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 241000588769 Proteus <enterobacteria> Species 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000238711 Pyroglyphidae Species 0.000 description 1
- 108090000944 RNA Helicases Proteins 0.000 description 1
- 102000004409 RNA Helicases Human genes 0.000 description 1
- 239000013614 RNA sample Substances 0.000 description 1
- 230000004570 RNA-binding Effects 0.000 description 1
- 238000003559 RNA-seq method Methods 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000711798 Rabies lyssavirus Species 0.000 description 1
- 241000702247 Reoviridae Species 0.000 description 1
- 241000725643 Respiratory syncytial virus Species 0.000 description 1
- 241000712907 Retroviridae Species 0.000 description 1
- 241000711931 Rhabdoviridae Species 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000606726 Rickettsia typhi Species 0.000 description 1
- 208000000705 Rift Valley Fever Diseases 0.000 description 1
- 241000710799 Rubella virus Species 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 241000315672 SARS coronavirus Species 0.000 description 1
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 description 1
- 229940044665 STING agonist Drugs 0.000 description 1
- 101100379247 Salmo trutta apoa1 gene Proteins 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 229910052772 Samarium Inorganic materials 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 241000242680 Schistosoma mansoni Species 0.000 description 1
- 241000209056 Secale Species 0.000 description 1
- 241000961587 Secoviridae Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000258242 Siphonaptera Species 0.000 description 1
- 240000006394 Sorghum bicolor Species 0.000 description 1
- 235000011684 Sorghum saccharatum Nutrition 0.000 description 1
- 241000605008 Spirillum Species 0.000 description 1
- 241000589973 Spirochaeta Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 240000006694 Stellaria media Species 0.000 description 1
- 241000194017 Streptococcus Species 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 108090000787 Subtilisin Proteins 0.000 description 1
- 241000205101 Sulfolobus Species 0.000 description 1
- 108010008038 Synthetic Vaccines Proteins 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000024932 T cell mediated immunity Effects 0.000 description 1
- 206010042971 T-cell lymphoma Diseases 0.000 description 1
- 208000026651 T-cell prolymphocytic leukemia Diseases 0.000 description 1
- 210000000662 T-lymphocyte subset Anatomy 0.000 description 1
- 108700019889 TEL-AML1 fusion Proteins 0.000 description 1
- 241000255628 Tabanidae Species 0.000 description 1
- 108010039185 Tenecteplase Proteins 0.000 description 1
- 101100242191 Tetraodon nigroviridis rho gene Proteins 0.000 description 1
- 210000000447 Th1 cell Anatomy 0.000 description 1
- 241000204667 Thermoplasma Species 0.000 description 1
- 241000605118 Thiobacillus Species 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- 102100036407 Thioredoxin Human genes 0.000 description 1
- 241000710771 Tick-borne encephalitis virus Species 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 241000710924 Togaviridae Species 0.000 description 1
- 102100039360 Toll-like receptor 4 Human genes 0.000 description 1
- 102100039390 Toll-like receptor 7 Human genes 0.000 description 1
- 102100033110 Toll-like receptor 8 Human genes 0.000 description 1
- NGBFQHCMQULJNZ-UHFFFAOYSA-N Torsemide Chemical compound CC(C)NC(=O)NS(=O)(=O)C1=CN=CC=C1NC1=CC=CC(C)=C1 NGBFQHCMQULJNZ-UHFFFAOYSA-N 0.000 description 1
- 241000710915 Totiviridae Species 0.000 description 1
- 241000223997 Toxoplasma gondii Species 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 241000589886 Treponema Species 0.000 description 1
- 241000224527 Trichomonas vaginalis Species 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 241000223105 Trypanosoma brucei Species 0.000 description 1
- 241000132125 Tyrophagus Species 0.000 description 1
- 108091023045 Untranslated Region Proteins 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 241000218215 Urticaceae Species 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 241000700618 Vaccinia virus Species 0.000 description 1
- 206010046865 Vaccinia virus infection Diseases 0.000 description 1
- SECKRCOLJRRGGV-UHFFFAOYSA-N Vardenafil Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(CC)CC1 SECKRCOLJRRGGV-UHFFFAOYSA-N 0.000 description 1
- 241000700647 Variola virus Species 0.000 description 1
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 1
- 241000607598 Vibrio Species 0.000 description 1
- 108700005077 Viral Genes Proteins 0.000 description 1
- MPFIISQEADXBEO-UHFFFAOYSA-M X-rhod-1 Chemical compound [Br-].CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C=2C3=CC=4CCCN5CCCC(C=45)=C3OC3=C4C5=[N+](CCC4)CCCC5=CC3=2)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O MPFIISQEADXBEO-UHFFFAOYSA-M 0.000 description 1
- 208000003152 Yellow Fever Diseases 0.000 description 1
- 241000607734 Yersinia <bacteria> Species 0.000 description 1
- GRRMZXFOOGQMFA-UHFFFAOYSA-J YoYo-1 Chemical compound [I-].[I-].[I-].[I-].C12=CC=CC=C2C(C=C2N(C3=CC=CC=C3O2)C)=CC=[N+]1CCC[N+](C)(C)CCC[N+](C)(C)CCC[N+](C1=CC=CC=C11)=CC=C1C=C1N(C)C2=CC=CC=C2O1 GRRMZXFOOGQMFA-UHFFFAOYSA-J 0.000 description 1
- JSBNEYNPYQFYNM-UHFFFAOYSA-J YoYo-3 Chemical compound [I-].[I-].[I-].[I-].C12=CC=CC=C2C(C=CC=C2N(C3=CC=CC=C3O2)C)=CC=[N+]1CCC(=[N+](C)C)CCCC(=[N+](C)C)CC[N+](C1=CC=CC=C11)=CC=C1C=CC=C1N(C)C2=CC=CC=C2O1 JSBNEYNPYQFYNM-UHFFFAOYSA-J 0.000 description 1
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 description 1
- 229920000392 Zymosan Polymers 0.000 description 1
- DSNRWDQKZIEDDB-GCMPNPAFSA-N [(2r)-3-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-2-[(z)-octadec-9-enoyl]oxypropyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C/CCCCCCCC DSNRWDQKZIEDDB-GCMPNPAFSA-N 0.000 description 1
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
- APERIXFHHNDFQV-UHFFFAOYSA-N [2-[2-[2-[bis(carboxymethyl)amino]-5-methylphenoxy]ethoxy]-4-[3,6-bis(dimethylamino)xanthen-9-ylidene]cyclohexa-2,5-dien-1-ylidene]-bis(carboxymethyl)azanium;chloride Chemical compound [Cl-].C12=CC=C(N(C)C)C=C2OC2=CC(N(C)C)=CC=C2C1=C(C=1)C=CC(=[N+](CC(O)=O)CC(O)=O)C=1OCCOC1=CC(C)=CC=C1N(CC(O)=O)CC(O)=O APERIXFHHNDFQV-UHFFFAOYSA-N 0.000 description 1
- 229960003697 abatacept Drugs 0.000 description 1
- 229960000446 abciximab Drugs 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 229960002122 acebutolol Drugs 0.000 description 1
- GOEMGAFJFRBGGG-UHFFFAOYSA-N acebutolol Chemical compound CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(C(C)=O)=C1 GOEMGAFJFRBGGG-UHFFFAOYSA-N 0.000 description 1
- 229940127024 acid based drug Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- DPKHZNPWBDQZCN-UHFFFAOYSA-N acridine orange free base Chemical compound C1=CC(N(C)C)=CC2=NC3=CC(N(C)C)=CC=C3C=C21 DPKHZNPWBDQZCN-UHFFFAOYSA-N 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000003044 adaptive effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 108010004469 allophycocyanin Proteins 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- 239000002160 alpha blocker Substances 0.000 description 1
- 229940124308 alpha-adrenoreceptor antagonist Drugs 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229960003318 alteplase Drugs 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000003957 anion exchange resin Substances 0.000 description 1
- 229960000983 anistreplase Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000000947 anti-immunosuppressive effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000005809 anti-tumor immunity Effects 0.000 description 1
- 239000003005 anticarcinogenic agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 238000009246 art therapy Methods 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 229940037642 autologous vaccine Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Natural products C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960004324 betaxolol Drugs 0.000 description 1
- CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 229920000080 bile acid sequestrant Polymers 0.000 description 1
- 229940096699 bile acid sequestrants Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 229960002781 bisoprolol Drugs 0.000 description 1
- VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 description 1
- 239000010836 blood and blood product Substances 0.000 description 1
- 229940125691 blood product Drugs 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229960004064 bumetanide Drugs 0.000 description 1
- MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- IDMLRIMDYVWWRJ-UHFFFAOYSA-N calcium crimson Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=CC=C1OCCOC1=CC(NS(=O)(=O)C=2C=C(C(C=3C4=CC=5CCCN6CCCC(C=56)=C4OC4=C5C6=[N+](CCC5)CCCC6=CC4=3)=CC=2)S([O-])(=O)=O)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O IDMLRIMDYVWWRJ-UHFFFAOYSA-N 0.000 description 1
- NMUGYJRMGWBCPU-UHFFFAOYSA-N calcium orange Chemical compound C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C(C(=C1)C([O-])=O)=CC=C1NC(=S)NC(C=1)=CC=C(N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O)C=1OCCOC1=CC=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O NMUGYJRMGWBCPU-UHFFFAOYSA-N 0.000 description 1
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 229960000932 candesartan Drugs 0.000 description 1
- SGZAIDDFHDDFJU-UHFFFAOYSA-N candesartan Chemical compound CCOC1=NC2=CC=CC(C(O)=O)=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SGZAIDDFHDDFJU-UHFFFAOYSA-N 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 238000005251 capillar electrophoresis Methods 0.000 description 1
- 238000001818 capillary gel electrophoresis Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000000496 cardiotonic agent Substances 0.000 description 1
- 230000003177 cardiotonic effect Effects 0.000 description 1
- 229960001222 carteolol Drugs 0.000 description 1
- LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- CZPLANDPABRVHX-UHFFFAOYSA-N cascade blue Chemical compound C=1C2=CC=CC=C2C(NCC)=CC=1C(C=1C=CC(=CC=1)N(CC)CC)=C1C=CC(=[N+](CC)CC)C=C1 CZPLANDPABRVHX-UHFFFAOYSA-N 0.000 description 1
- PTIUZRZHZRYCJE-UHFFFAOYSA-N cascade yellow Chemical compound C1=C(S([O-])(=O)=O)C(OC)=CC=C1C1=CN=C(C=2C=C[N+](CC=3C=C(C=CC=3)C(=O)ON3C(CCC3=O)=O)=CC=2)O1 PTIUZRZHZRYCJE-UHFFFAOYSA-N 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 229960002412 cediranib Drugs 0.000 description 1
- 229940047495 celebrex Drugs 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000010307 cell transformation Effects 0.000 description 1
- 108091092328 cellular RNA Proteins 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229960002155 chlorothiazide Drugs 0.000 description 1
- 229960001523 chlortalidone Drugs 0.000 description 1
- 230000001906 cholesterol absorption Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 229960004588 cilostazol Drugs 0.000 description 1
- RRGUKTPIGVIEKM-UHFFFAOYSA-N cilostazol Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 RRGUKTPIGVIEKM-UHFFFAOYSA-N 0.000 description 1
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 230000008045 co-localization Effects 0.000 description 1
- 229960001152 colesevelam Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 229940047120 colony stimulating factors Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 230000009918 complex formation Effects 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000001218 confocal laser scanning microscopy Methods 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000011258 core-shell material Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000016396 cytokine production Effects 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000007402 cytotoxic response Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 229960004969 dalteparin Drugs 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000004041 dendritic cell maturation Effects 0.000 description 1
- 229940029030 dendritic cell vaccine Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- JLIOTPLALDYAEH-UHFFFAOYSA-M diIC18(7) dye Chemical compound [I-].CC1(C)C2=CC=CC=C2N(CCCCCCCCCCCCCCCCCC)C1=CC=CC=CC=CC1=[N+](CCCCCCCCCCCCCCCCCC)C2=CC=CC=C2C1(C)C JLIOTPLALDYAEH-UHFFFAOYSA-M 0.000 description 1
- GFZPJHFJZGRWMQ-UHFFFAOYSA-M diOC18(3) dye Chemical compound [O-]Cl(=O)(=O)=O.O1C2=CC=CC=C2[N+](CCCCCCCCCCCCCCCCCC)=C1C=CC=C1N(CCCCCCCCCCCCCCCCCC)C2=CC=CC=C2O1 GFZPJHFJZGRWMQ-UHFFFAOYSA-M 0.000 description 1
- 238000002059 diagnostic imaging Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 239000005546 dideoxynucleotide Substances 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- LHCZDUCPSRJDJT-UHFFFAOYSA-N dilauroyl phosphatidylglycerol Chemical compound CCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCC LHCZDUCPSRJDJT-UHFFFAOYSA-N 0.000 description 1
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 description 1
- 229960004166 diltiazem Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 229960003724 dimyristoylphosphatidylcholine Drugs 0.000 description 1
- 229960005160 dimyristoylphosphatidylglycerol Drugs 0.000 description 1
- 229960002768 dipyridamole Drugs 0.000 description 1
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
- 239000002988 disease modifying antirheumatic drug Substances 0.000 description 1
- 229960001066 disopyramide Drugs 0.000 description 1
- UVTNFZQICZKOEM-UHFFFAOYSA-N disopyramide Chemical compound C=1C=CC=NC=1C(C(N)=O)(CCN(C(C)C)C(C)C)C1=CC=CC=C1 UVTNFZQICZKOEM-UHFFFAOYSA-N 0.000 description 1
- BPHQZTVXXXJVHI-AJQTZOPKSA-N ditetradecanoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-AJQTZOPKSA-N 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- IXTMWRCNAAVVAI-UHFFFAOYSA-N dofetilide Chemical compound C=1C=C(NS(C)(=O)=O)C=CC=1CCN(C)CCOC1=CC=C(NS(C)(=O)=O)C=C1 IXTMWRCNAAVVAI-UHFFFAOYSA-N 0.000 description 1
- 229960002994 dofetilide Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 description 1
- 229960001389 doxazosin Drugs 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- KBQHZAAAGSGFKK-UHFFFAOYSA-N dysprosium atom Chemical compound [Dy] KBQHZAAAGSGFKK-UHFFFAOYSA-N 0.000 description 1
- 201000009028 early myoclonic encephalopathy Diseases 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960000610 enoxaparin Drugs 0.000 description 1
- 239000005447 environmental material Substances 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 238000003114 enzyme-linked immunosorbent spot assay Methods 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 229960004563 eprosartan Drugs 0.000 description 1
- OROAFUQRIXKEMV-LDADJPATSA-N eprosartan Chemical compound C=1C=C(C(O)=O)C=CC=1CN1C(CCCC)=NC=C1\C=C(C(O)=O)/CC1=CC=CS1 OROAFUQRIXKEMV-LDADJPATSA-N 0.000 description 1
- 229960004468 eptifibatide Drugs 0.000 description 1
- GLGOPUHVAZCPRB-LROMGURASA-N eptifibatide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCCNC(=N)N)NC(=O)CCSSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]1CC1=CN=C2[C]1C=CC=C2 GLGOPUHVAZCPRB-LROMGURASA-N 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- UYAHIZSMUZPPFV-UHFFFAOYSA-N erbium Chemical compound [Er] UYAHIZSMUZPPFV-UHFFFAOYSA-N 0.000 description 1
- 229960003745 esmolol Drugs 0.000 description 1
- AQNDDEOPVVGCPG-UHFFFAOYSA-N esmolol Chemical compound COC(=O)CCC1=CC=C(OCC(O)CNC(C)C)C=C1 AQNDDEOPVVGCPG-UHFFFAOYSA-N 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- AVOLMBLBETYQHX-UHFFFAOYSA-N etacrynic acid Chemical compound CCC(=C)C(=O)C1=CC=C(OCC(O)=O)C(Cl)=C1Cl AVOLMBLBETYQHX-UHFFFAOYSA-N 0.000 description 1
- 229960003199 etacrynic acid Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- ZMMJGEGLRURXTF-UHFFFAOYSA-N ethidium bromide Chemical compound [Br-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CC)=C1C1=CC=CC=C1 ZMMJGEGLRURXTF-UHFFFAOYSA-N 0.000 description 1
- 229960005542 ethidium bromide Drugs 0.000 description 1
- OGPBJKLSAFTDLK-UHFFFAOYSA-N europium atom Chemical compound [Eu] OGPBJKLSAFTDLK-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 229940125753 fibrate Drugs 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 229960000449 flecainide Drugs 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 108091006047 fluorescent proteins Proteins 0.000 description 1
- 102000034287 fluorescent proteins Human genes 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 108020005243 folate receptor Proteins 0.000 description 1
- 102000006815 folate receptor Human genes 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 210000000285 follicular dendritic cell Anatomy 0.000 description 1
- KANJSNBRCNMZMV-ABRZTLGGSA-N fondaparinux Chemical compound O[C@@H]1[C@@H](NS(O)(=O)=O)[C@@H](OC)O[C@H](COS(O)(=O)=O)[C@H]1O[C@H]1[C@H](OS(O)(=O)=O)[C@@H](O)[C@H](O[C@@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O[C@@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O4)NS(O)(=O)=O)[C@H](O3)C(O)=O)O)[C@@H](COS(O)(=O)=O)O2)NS(O)(=O)=O)[C@H](C(O)=O)O1 KANJSNBRCNMZMV-ABRZTLGGSA-N 0.000 description 1
- 229960001318 fondaparinux Drugs 0.000 description 1
- 239000013568 food allergen Substances 0.000 description 1
- 231100000221 frame shift mutation induction Toxicity 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- YFHXZQPUBCBNIP-UHFFFAOYSA-N fura-2 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=3OC(=CC=3C=2)C=2OC(=CN=2)C(O)=O)N(CC(O)=O)CC(O)=O)=C1 YFHXZQPUBCBNIP-UHFFFAOYSA-N 0.000 description 1
- 229960003883 furosemide Drugs 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 231100000118 genetic alteration Toxicity 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 210000004602 germ cell Anatomy 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 229930182470 glycoside Natural products 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000013574 grass pollen allergen Substances 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 229960004553 guanabenz Drugs 0.000 description 1
- 229960002048 guanfacine Drugs 0.000 description 1
- 238000003505 heat denaturation Methods 0.000 description 1
- 244000000013 helminth Species 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- KJZYNXUDTRRSPN-UHFFFAOYSA-N holmium atom Chemical compound [Ho] KJZYNXUDTRRSPN-UHFFFAOYSA-N 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940046533 house dust mites Drugs 0.000 description 1
- 102000053786 human PCSK9 Human genes 0.000 description 1
- 102000050022 human STING1 Human genes 0.000 description 1
- 230000004727 humoral immunity Effects 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- 229960002474 hydralazine Drugs 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
- 229960004171 hydroxychloroquine Drugs 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 229960004053 ibutilide Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 239000000568 immunological adjuvant Substances 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 230000000091 immunopotentiator Effects 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- PNDZEEPOYCVIIY-UHFFFAOYSA-N indo-1 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C=2N=C3[CH]C(=CC=C3C=2)C(O)=O)N(CC(O)=O)CC(O)=O)=C1 PNDZEEPOYCVIIY-UHFFFAOYSA-N 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000031146 intracellular signal transduction Effects 0.000 description 1
- 102000008371 intracellularly ATP-gated chloride channel activity proteins Human genes 0.000 description 1
- 230000002601 intratumoral effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
- 229960004427 isradipine Drugs 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 229960001632 labetalol Drugs 0.000 description 1
- 238000002356 laser light scattering Methods 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 239000002960 lipid emulsion Substances 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 1
- 230000007108 local immune response Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002171 loop diuretic Substances 0.000 description 1
- 229960004773 losartan Drugs 0.000 description 1
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- RPKCZJYDUKVMGF-UHFFFAOYSA-L lucifer yellow carbohydrazide dye Chemical compound [Li+].[Li+].[O-]S(=O)(=O)C1=CC(C(N(NC(=O)NN)C2=O)=O)=C3C2=CC(S([O-])(=O)=O)=CC3=C1N RPKCZJYDUKVMGF-UHFFFAOYSA-L 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 208000001419 lymphocytic choriomeningitis Diseases 0.000 description 1
- 210000005210 lymphoid organ Anatomy 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 108010051618 macrophage stimulatory lipopeptide 2 Proteins 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- NGCVJRFIBJVSFI-UHFFFAOYSA-I magnesium green Chemical compound [K+].[K+].[K+].[K+].[K+].C1=C(N(CC([O-])=O)CC([O-])=O)C(OCC(=O)[O-])=CC(NC(=O)C=2C=C3C(C4(C5=CC(Cl)=C([O-])C=C5OC5=CC([O-])=C(Cl)C=C54)OC3=O)=CC=2)=C1 NGCVJRFIBJVSFI-UHFFFAOYSA-I 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 201000004792 malaria Diseases 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000001840 matrix-assisted laser desorption--ionisation time-of-flight mass spectrometry Methods 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- IMYZQPCYWPFTAG-IQJOONFLSA-N mecamylamine Chemical compound C1C[C@@H]2C(C)(C)[C@@](NC)(C)[C@H]1C2 IMYZQPCYWPFTAG-IQJOONFLSA-N 0.000 description 1
- 229960002525 mecamylamine Drugs 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229960001810 meprednisone Drugs 0.000 description 1
- PIDANAQULIKBQS-RNUIGHNZSA-N meprednisone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)CC2=O PIDANAQULIKBQS-RNUIGHNZSA-N 0.000 description 1
- 210000003936 merozoite Anatomy 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002082 metal nanoparticle Substances 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 1
- 229960003739 methyclothiazide Drugs 0.000 description 1
- VKQFCGNPDRICFG-UHFFFAOYSA-N methyl 2-methylpropyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1C1=CC=CC=C1[N+]([O-])=O VKQFCGNPDRICFG-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960002817 metolazone Drugs 0.000 description 1
- AQCHWTWZEMGIFD-UHFFFAOYSA-N metolazone Chemical compound CC1NC2=CC(Cl)=C(S(N)(=O)=O)C=C2C(=O)N1C1=CC=CC=C1C AQCHWTWZEMGIFD-UHFFFAOYSA-N 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- 229960003404 mexiletine Drugs 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 229960003632 minoxidil Drugs 0.000 description 1
- FZTMEYOUQQFBJR-UHFFFAOYSA-M mitoTracker Orange Chemical compound [Cl-].C=12C=CC(=[N+](C)C)C=C2OC2=CC(N(C)C)=CC=C2C=1C1=CC=C(CCl)C=C1 FZTMEYOUQQFBJR-UHFFFAOYSA-M 0.000 description 1
- IKEOZQLIVHGQLJ-UHFFFAOYSA-M mitoTracker Red Chemical compound [Cl-].C1=CC(CCl)=CC=C1C(C1=CC=2CCCN3CCCC(C=23)=C1O1)=C2C1=C(CCC1)C3=[N+]1CCCC3=C2 IKEOZQLIVHGQLJ-UHFFFAOYSA-M 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- AHEWZZJEDQVLOP-UHFFFAOYSA-N monobromobimane Chemical compound BrCC1=C(C)C(=O)N2N1C(C)=C(C)C2=O AHEWZZJEDQVLOP-UHFFFAOYSA-N 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 208000010805 mumps infectious disease Diseases 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 229960004255 nadolol Drugs 0.000 description 1
- VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 1
- 229960000899 nadroparin Drugs 0.000 description 1
- 210000004296 naive t lymphocyte Anatomy 0.000 description 1
- 239000002121 nanofiber Substances 0.000 description 1
- 229940039328 nanoparticle-based vaccine Drugs 0.000 description 1
- 239000002072 nanorope Substances 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 210000001989 nasopharynx Anatomy 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 210000005170 neoplastic cell Anatomy 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 229960001783 nicardipine Drugs 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- VOFUROIFQGPCGE-UHFFFAOYSA-N nile red Chemical compound C1=CC=C2C3=NC4=CC=C(N(CC)CC)C=C4OC3=CC(=O)C2=C1 VOFUROIFQGPCGE-UHFFFAOYSA-N 0.000 description 1
- 229960000715 nimodipine Drugs 0.000 description 1
- 229960000227 nisoldipine Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000011330 nucleic acid test Methods 0.000 description 1
- 239000002417 nutraceutical Substances 0.000 description 1
- 235000021436 nutraceutical agent Nutrition 0.000 description 1
- VQWNELVFHZRFIB-UHFFFAOYSA-N odn 1826 Chemical compound O=C1NC(=O)C(C)=CN1C(O1)CC(O)C1COP(O)(=O)OC1CC(N2C(NC(=O)C(C)=C2)=O)OC1COP(O)(=O)OC1CC(N2C3=C(C(NC(N)=N3)=O)N=C2)OC1COP(O)(=O)OC1CC(N2C(N=C(N)C=C2)=O)OC1COP(O)(=O)OC1CC(N2C3=NC=NC(N)=C3N=C2)OC1COP(O)(=O)OC1CC(N2C3=C(C(NC(N)=N3)=O)N=C2)OC1COP(O)(=O)OC1CC(N2C(NC(=O)C(C)=C2)=O)OC1COP(O)(=O)OC1CC(N2C(N=C(N)C=C2)=O)OC1COP(O)(=O)OC1CC(N2C(N=C(N)C=C2)=O)OC1COP(O)(=O)OC1CC(N2C(NC(=O)C(C)=C2)=O)OC1COP(O)(=O)OC(C(O1)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(O)=O)CC1N1C=C(C)C(=O)NC1=O VQWNELVFHZRFIB-UHFFFAOYSA-N 0.000 description 1
- 229940046166 oligodeoxynucleotide Drugs 0.000 description 1
- 229960001199 olmesartan medoxomil Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- VYNDHICBIRRPFP-UHFFFAOYSA-N pacific blue Chemical compound FC1=C(O)C(F)=C2OC(=O)C(C(=O)O)=CC2=C1 VYNDHICBIRRPFP-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PIRWNASAJNPKHT-SHZATDIYSA-N pamp Chemical compound C([C@@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)N)C(C)C)C1=CC=CC=C1 PIRWNASAJNPKHT-SHZATDIYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 239000013610 patient sample Substances 0.000 description 1
- 229960000639 pazopanib Drugs 0.000 description 1
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229960002035 penbutolol Drugs 0.000 description 1
- KQXKVJAGOJTNJS-HNNXBMFYSA-N penbutolol Chemical compound CC(C)(C)NC[C@H](O)COC1=CC=CC=C1C1CCCC1 KQXKVJAGOJTNJS-HNNXBMFYSA-N 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 229960002582 perindopril Drugs 0.000 description 1
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 229960003418 phenoxybenzamine Drugs 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 239000006069 physical mixture Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 description 1
- 229960002508 pindolol Drugs 0.000 description 1
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229940115272 polyinosinic:polycytidylic acid Drugs 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 229960005483 polythiazide Drugs 0.000 description 1
- 229920000046 polythiazide Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000003450 potassium channel blocker Substances 0.000 description 1
- 239000003286 potassium sparing diuretic agent Substances 0.000 description 1
- 229940097241 potassium-sparing diuretic Drugs 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 229960000244 procainamide Drugs 0.000 description 1
- REQCZEXYDRLIBE-UHFFFAOYSA-N procainamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 REQCZEXYDRLIBE-UHFFFAOYSA-N 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 235000013930 proline Nutrition 0.000 description 1
- 125000001500 prolyl group Chemical class [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- JWHAUXFOSRPERK-UHFFFAOYSA-N propafenone Chemical compound CCCNCC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1 JWHAUXFOSRPERK-UHFFFAOYSA-N 0.000 description 1
- 229960000203 propafenone Drugs 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 229940023143 protein vaccine Drugs 0.000 description 1
- 230000003161 proteinsynthetic effect Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000000575 proteomic method Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 238000012175 pyrosequencing Methods 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010223 real-time analysis Methods 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 108010051412 reteplase Proteins 0.000 description 1
- 229960002917 reteplase Drugs 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 229960005496 reviparin Drugs 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 1
- MYFATKRONKHHQL-UHFFFAOYSA-N rhodamine 123 Chemical compound [Cl-].COC(=O)C1=CC=CC=C1C1=C2C=CC(=[NH2+])C=C2OC2=CC(N)=CC=C21 MYFATKRONKHHQL-UHFFFAOYSA-N 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 108010078070 scavenger receptors Proteins 0.000 description 1
- 102000014452 scavenger receptors Human genes 0.000 description 1
- 208000011581 secondary neoplasm Diseases 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000009919 sequestration Effects 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 229960003310 sildenafil Drugs 0.000 description 1
- 239000002924 silencing RNA Substances 0.000 description 1
- 230000001743 silencing effect Effects 0.000 description 1
- 229960002855 simvastatin Drugs 0.000 description 1
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 description 1
- 238000004557 single molecule detection Methods 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000003195 sodium channel blocking agent Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- ZSOMPVKQDGLTOT-UHFFFAOYSA-J sodium green Chemical compound C[N+](C)(C)C.C[N+](C)(C)C.C[N+](C)(C)C.C[N+](C)(C)C.COC=1C=C(NC(=O)C=2C=C(C(=CC=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC([O-])=C(Cl)C=C32)C([O-])=O)C(OC)=CC=1N(CCOCC1)CCOCCOCCN1C(C(=C1)OC)=CC(OC)=C1NC(=O)C1=CC=C(C2=C3C=C(Cl)C(=O)C=C3OC3=CC([O-])=C(Cl)C=C32)C(C([O-])=O)=C1 ZSOMPVKQDGLTOT-UHFFFAOYSA-J 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 210000004988 splenocyte Anatomy 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 229960003329 sulfinpyrazone Drugs 0.000 description 1
- MBGGBVCUIVRRBF-UHFFFAOYSA-N sulfinpyrazone Chemical compound O=C1N(C=2C=CC=CC=2)N(C=2C=CC=CC=2)C(=O)C1CCS(=O)C1=CC=CC=C1 MBGGBVCUIVRRBF-UHFFFAOYSA-N 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 229960000835 tadalafil Drugs 0.000 description 1
- IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 description 1
- 238000004885 tandem mass spectrometry Methods 0.000 description 1
- 229960000651 tasosartan Drugs 0.000 description 1
- ADXGNEYLLLSOAR-UHFFFAOYSA-N tasosartan Chemical compound C12=NC(C)=NC(C)=C2CCC(=O)N1CC(C=C1)=CC=C1C1=CC=CC=C1C=1N=NNN=1 ADXGNEYLLLSOAR-UHFFFAOYSA-N 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- 229960000216 tenecteplase Drugs 0.000 description 1
- VCKUSRYTPJJLNI-UHFFFAOYSA-N terazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1CCCO1 VCKUSRYTPJJLNI-UHFFFAOYSA-N 0.000 description 1
- 229960001693 terazosin Drugs 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- WGTODYJZXSJIAG-UHFFFAOYSA-N tetramethylrhodamine chloride Chemical compound [Cl-].C=12C=CC(N(C)C)=CC2=[O+]C2=CC(N(C)C)=CC=C2C=1C1=CC=CC=C1C(O)=O WGTODYJZXSJIAG-UHFFFAOYSA-N 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical group [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 108060008226 thioredoxin Proteins 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- 229960000103 thrombolytic agent Drugs 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 230000002992 thymic effect Effects 0.000 description 1
- 210000002303 tibia Anatomy 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 229960005062 tinzaparin Drugs 0.000 description 1
- 229960003425 tirofiban Drugs 0.000 description 1
- COKMIXFXJJXBQG-NRFANRHFSA-N tirofiban Chemical compound C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 COKMIXFXJJXBQG-NRFANRHFSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229960005461 torasemide Drugs 0.000 description 1
- 229960004380 tramadol Drugs 0.000 description 1
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 230000005030 transcription termination Effects 0.000 description 1
- 230000014621 translational initiation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 229940046536 tree pollen allergenic extract Drugs 0.000 description 1
- 229950007217 tremelimumab Drugs 0.000 description 1
- 229960004813 trichlormethiazide Drugs 0.000 description 1
- LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 1
- 230000037455 tumor specific immune response Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 238000012285 ultrasound imaging Methods 0.000 description 1
- 230000004222 uncontrolled growth Effects 0.000 description 1
- 241000701447 unidentified baculovirus Species 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 210000003708 urethra Anatomy 0.000 description 1
- 210000003932 urinary bladder Anatomy 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 229940124931 vaccine adjuvant Drugs 0.000 description 1
- 208000007089 vaccinia Diseases 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
- 229960002381 vardenafil Drugs 0.000 description 1
- 239000004066 vascular targeting agent Substances 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 229960005080 warfarin Drugs 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000002424 x-ray crystallography Methods 0.000 description 1
- 150000003732 xanthenes Chemical class 0.000 description 1
- JNELGWHKGNBSMD-UHFFFAOYSA-N xanthone Chemical class C1=CC=C2C(=O)C3=CC=CC=C3OC2=C1 JNELGWHKGNBSMD-UHFFFAOYSA-N 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/712—Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001103—Receptors for growth factors
- A61K39/001106—Her-2/neu/ErbB2, Her-3/ErbB3 or Her 4/ErbB4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001102—Receptors, cell surface antigens or cell surface determinants
- A61K39/001103—Receptors for growth factors
- A61K39/00111—Hepatocyte growth factor receptor [HGFR or c-met]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/00113—Growth factors
- A61K39/001132—Fibroblast growth factors [FGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001148—Regulators of development
- A61K39/00115—Apoptosis related proteins, e.g. survivin or livin
- A61K39/001151—Apoptosis related proteins, e.g. survivin or livin p53
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001154—Enzymes
- A61K39/001156—Tyrosinase and tyrosinase related proteinases [TRP-1 or TRP-2]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001154—Enzymes
- A61K39/001157—Telomerase or TERT [telomerase reverse transcriptase]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001154—Enzymes
- A61K39/001162—Kinases, e.g. Raf or Src
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001154—Enzymes
- A61K39/001164—GTPases, e.g. Ras or Rho
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001166—Adhesion molecules, e.g. NRCAM, EpCAM or cadherins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001176—Heat shock proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/00118—Cancer antigens from embryonic or fetal origin
- A61K39/001181—Alpha-feto protein
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/00118—Cancer antigens from embryonic or fetal origin
- A61K39/001182—Carcinoembryonic antigen [CEA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001184—Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001184—Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
- A61K39/001186—MAGE
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001184—Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
- A61K39/001188—NY-ESO
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001184—Cancer testis antigens, e.g. SSX, BAGE, GAGE or SAGE
- A61K39/001189—PRAME
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/00119—Melanoma antigens
- A61K39/001191—Melan-A/MART
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/00119—Melanoma antigens
- A61K39/001192—Glycoprotein 100 [Gp100]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001193—Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; PAP or PSGR
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001193—Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; PAP or PSGR
- A61K39/001194—Prostate specific antigen [PSA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001193—Prostate associated antigens e.g. Prostate stem cell antigen [PSCA]; Prostate carcinoma tumor antigen [PCTA]; PAP or PSGR
- A61K39/001195—Prostate specific membrane antigen [PSMA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0011—Cancer antigens
- A61K39/001196—Fusion proteins originating from gene translocation in cancer cells
- A61K39/001197—Breakpoint cluster region-abelson tyrosine kinase [BCR-ABL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/554—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being a steroid plant sterol, glycyrrhetic acid, enoxolone or bile acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
- A61K47/6917—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a lipoprotein vesicle, e.g. HDL or LDL proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/111—General methods applicable to biologically active non-coding nucleic acids
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/14—Type of nucleic acid interfering N.A.
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/35—Nature of the modification
- C12N2310/351—Conjugate
- C12N2310/3515—Lipophilic moiety, e.g. cholesterol
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Mycology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Cell Biology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Developmental Biology & Embryology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Dispersion Chemistry (AREA)
- Pregnancy & Childbirth (AREA)
- Reproductive Health (AREA)
- Gynecology & Obstetrics (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Inorganic Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Botany (AREA)
Description
本発明は、2015年3月25日に出願された米国仮特許出願第62/138,186号及び2015年10月30日に出願された米国仮特許出願第62/248,908号の優先権を主張し、これらは、全体として参照により組み込まれる。
連邦政府による資金提供を受けた研究開発の記載
本発明は、米国国立衛生研究所により授与されたAI097291に基づく政府の支援によりなされた。政府は、本発明に特定の権利を有する。
al.J.Clin.Invest.115,739-746(2005);Fourcade,J.et al.J.Immunother.31,781-791(2008)を参照のこと)。さらに、ナノディスクプラットフォームは、ネオアンチゲンに容易に適合することができ、強力な抗腫瘍免疫を生じることが示された。このような結果は、癌免疫療法のための新しい強力なアプローチであり、より概括的は、個別化ナノ医薬品に対する一般的な方策を示唆する。
ナノ粒子
本発明は、種々のタイプの障害を、処置、予防、または改善するために構成された生体高分子薬と複合化するための具体的なタイプまたは種類のナノ粒子に限定されない。
RNA干渉
特定の実施形態では、sHDLナノ粒子は、RNA干渉の方法及びシステム内で使用される。
States of America 2004,101(18),7100-7105;Dadu,R.T.;et al.,Nature Reviews Cardiology 2014,11(10),563-575;Horton,J.D.;et al.,Trends in Biochemical Sciences 2007,32(2),71-77を参照のこと)。それ故、PCSK9阻害は、LDL-Cを潜在的に減少させる可能性がある(例えば、Shen,L.;et al.,Pharmacological Research 2013,73,27-34を参照のこと)。インビボでのPCSK9阻害のために開発中の治療的アプローチは、PCSK9のsiRNA媒介性ノックダウン及びPCSK9に対するワクチン接種を含む(例えば、Fitzgerald,K.;et al.,Lancet 2014,383(9911),60-68;Galabova,G.;et al.,Circulation 2013,128(22)を参照のこと)が、両方の方策は、各方策のインビボでの効能を最大化するために、いかに治療薬を標的細胞に、すなわち、それぞれ肝細胞及び免疫細胞に効果的に送達するかという主要な課題に直面する。
siRNAを細胞に導入することを含み、PCSK9 siRNAは、互いに相補的な2つのRNA鎖を含み、PCSK9 siRNAは、sHDLナノ粒子内に封入されている。一部の実施形態では、PCSK9 siRNAは、3’センス鎖でコレステロールにより修飾される。一部の実施形態では、細胞は、ヒト内にある。
免疫応答刺激
免疫系は、2つの機能的サブシステム:自然免疫系及び獲得免疫系に分類することができる。自然免疫系は、感染に対する防御の最前線であり、ほとんどの潜在的な病原体は、例えば、顕著な感染を引き起こし得る前に、この系により急速に無力化される。獲得免疫系は、侵入生体の、抗原と称される分子構造に反応する。獲得免疫反応の2つのタイプ:体液性免疫反応及び細胞性免疫反応がある。体液性免疫反応では、体液にB細胞により分泌された抗体は、病原体由来の抗原に結合して、様々な機序、例えば、補体媒介性の溶解により病原体の排除をもたらす。細胞媒介性免疫反応では、他の細胞を破壊することができるT細胞が活性化される。例えば、疾患に関連するタンパク質は、細胞中に存在する場合、細胞内でペプチドにタンパク質分解的に断片化される。次に、特定の細胞タンパク質は、このように形成された抗原またはペプチドに自らを付着させ、細胞の表面に輸送され、身体の分子防御機構、特に、T細胞に提示される。細胞傷害性T細胞は、これらの抗原を認識し、抗原を保有する細胞を死滅させる。
al.Arterioscler.Thromb.Vasc.Biol.33,2202-2211(2013);Fischer,N.O.et al.J.Am.Chem.Soc.135,2044-2047(2013);Tardy,C.et al.Atherosclerosis 232,110-118(2014);Duivenvoorden,R.et al.Nat.Commun.5,3065(2014)を参照のこと)と比較して、内因性ApoA-Iと配列相同性がないApoA1のリピートαヘリックスドメインに由来する22merのペプチド(22A)を有するsHDLナノディスクを合成した(例えば、米国特許第6,734,169号;米国特許第8,378,068号;Li,D.,Gordon,S.,Schwendeman,A.& Remaley,A.T.Apolipoprotein mimetic peptides
for stimulating cholesterol efflux.in Apolipoprotein Mimetics in the Management
of Human Disease(eds.Anantharamaiah,G.M.& Goldberg,D.)29-42(Springer,Switzerland,2015)を参照のこと)。それにより、自己免疫の潜在的誘発を回避した。重要なことに、sHDLは以前に、臨床試験用に製造されており、ヒトでは約2.2g/m2の最大許容用量で安全であることが証明されており(例えば、Khan,M.,et al.,Circulation 108(Suppl IV),563-564(2003);Miles,J.,et al.Proceedings of Arteriosclerosis Thrombosis and Vascular Biology
24,E19-E19(2004)を参照のこと)、値は、臨床試験における大部分の高分子または無機ナノ粒子より1~2桁大きい(例えば、Alexis,F.,et al.,Mol.Pharm.5,505-515(2008);Anselmo,A.C.& Mitragotri,S.A,AAPS J 17,1041-1054(2015)を参照のこと)。
ricketsii、Rickettsia typhi、Mycoplasma pneumoniae、Chlamydial psittaci、Chlamydial
trachomatis、Plasmodium falciparum、Trypanosoma brucei、Entamoeba histolytica、Toxoplasma gondii、Trichomonas vaginalis、及びSchistosoma mansoniに由来する抗原から得ることができる。これらは、胞子虫抗原、プラスモディアン(Plasmodian)抗原、例えば、マラリア原虫スポロゾイト表面タンパク質、スポロゾイト表面タンパク質、肝臓ステージ抗原、頂端膜会合タンパク質、またはメロゾイト表面タンパク質の全部または一部を含む。
synthesis.I.The synthesis of a tetrapeptide.J.Am.Chem.Soc.85:2149-54,1963)。
81:5662-5066(1984)及び米国特許第4,588,585号を参照のこと。
the Vascular Disrupting Agent 5,6-Dimethylxanthenone-4-Acetic Acid,Journal of Immunology,190:5216-25及びKim et al.(2013)Anticancer Flavonoids are Mouse-Selective
STING Agonists,8:1396-1401を参照のこと)。有用なアジュバントの他の例としては、化学的に修飾されたCpG(例えばCpR、Idera)、Poly(I:C)(例えばpolyi:CI2U)、非CpG細菌のDNAまたはRNA、ならびに免疫活性小分子ならびにシクロホスファミド、スニチニブ、ベバシズマブ、セレブレックス、NCX-4016、シルデナフィル、タダラフィル、バルデナフィル、ソラフィニブ、XL-999、CP-547632、パゾパニブ、ZD2171、AZD2171、イピリムマブ、トレメリムマブ、及びSC58175などの抗体が挙げられるが、これらに限定されず、これらは、治療的にかつ/またはアジュバントとして作用することがある。本発明の文脈において有用なアジュバント及び添加剤の量及び濃度は、過度の実験を行うことなく当業者が容易に決定することができる。さらなるアジュバントは、コロニー刺激因子、例えば、顆粒球マクロファージコロニー刺激因子(GM-CSF、サルラモスチム)を含む。
Delivery Reviews 2011,63(10-11),943-955を参照のこと)。
さらなる実施形態
特定の実施形態では、本明細書に記載されるような(例えば、RNA干渉のために構成された)(例えば、免疫応答を活性化するように構成された)sHDLナノ粒子は、1つ以上の治療薬を封入する。このような実施形態は、特定のタイプまたは種類の治療薬に限定されない。
Green、Marina Blue、Mitotracker Green FM、Mitotracker Orange CMTMRos、MitoTracker Red CMXRos、Monobromobimane、NBD amines、NeruoTrace 500/525 green、Nile red、Oregon Green、Pacific Blue、POP-1、Propidium iodide、ローダミン110、ローダミンレッド、R-フィコシアニン、Resorfin、RH414、Rhod-2、ローダミングリーン、ローダミン123、ROX dye、Sodium Green、SYTO blue(各種)、SYTO green(各種)、SYTO orange(各種)、SYTOX blue、SYTOX green、SYTOX orange、テトラメチルローダミンB、TOT-1、TOT-3、X-rhod-1、YOYO-1、YOYO-3が挙げられるが、これらに限定されない。一部の実施形態では、セラミドは、イメージング薬として提供される。一部の実施形態では、S1Pアゴニストは、イメージング薬として提供される。
実施例1.
本実施例は、生体高分子が充填されたsHDLの合成のための材料及び方法について記載する。
材料
1,2-ジミリストイル-sn-グリセロ-3-ホスホコリン(DMPC)、1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミン(DOPE)、及びローダミン(RHOD)標識DOPE(DOPE-RHOD)を全て、Avanti Polar Lipids(アラバマ州アラバスター)から購入した。ジオレオイル-sn-グリセロ-3-ホスホエタノールアミン-N-[3-(2-ピリジルジチオ)プロピオネート](DOPE-PDP)を、さらに合成した。使用されるHDL模倣ペプチド(22A;配列番号4)、SIINFEKL(配列番号341)、CSSSIINFEKL(配列番号342)、及びFITC標識CSSSIINFEK(FITC)Lを含む全てのペプチドを、Gen Scriptでカスタマイズした。オリゴデオキシヌクレオチドTLR9リガンドCpG1826(5’-tccatgacgttcctgacgtt-3’、小文字は、ホスホロチオエート骨格を表す)(配列番号343)及びコレステロール修飾CpG1826(5’-tccatgacgttcctgacgtt-3’-TEG-コレステロール)を、Intregrated DNA Technologiesに注文した。メタノール及びアセトニトリルなどのHPLCグレードの溶媒を、fisher scientificから購入した。ウシ胎児血清(FBS)、ペニシリン-ストレプトマイシン、β-メルカプトエタノール、及びACK溶解緩衝液を、Life Technologies(ニューヨーク州グランドアイランド)から購入した。顆粒球マクロファージコロニー刺激因子(GM-CSF)は、PeproTech(ニュージャージー州ロッキーヒル)の製品であった。ラット抗マウスCD16/32、CD86-PE、CD40-APC、SIINFEKL H-2Kb-PE及びMHCクラスII-FITCを、eBioscience(カルフォルニア州サンディエゴ)から入手した。ラット抗マウスCD8-APC、ハムスター抗マウスCD11c-PE、及びストレプトアビジン-Cy7を、BD Bioscience(カルフォルニア州サンノゼ)から入手した。iTAg tetramer/PE-H-2Kb OVA(SIINFEKL)を、Beckman Coulter(カルフォルニア州ブレア)から購入した。
ペプチド、核酸、または糖脂質が充填されたsHDLナノ粒子の調製。
sHDL製剤を、PBSで0.5mg/mLの22Aに希釈し、サイズを、動的光散乱(DLS、Zetasizer Nano ZSP、Malvern、英国)で測定した。元のサンプルを適切に希釈した後、透過型電子顕微鏡(TEM)により、sHDLのモルホロジーを観察した。
骨髄由来樹状細胞(BMDC)の調製
BMDCを、調製した。要約すると、マウスの大腿骨及び脛骨を、BMDC培養培地(10%のFBS、1%のペニシリン-ストレプトマイシン、50μMのβ-メルカプトエタノール、及び20ng/mlのGM-CSFを補充したRPMI 1640)で採取し、洗浄し、粉砕した。細胞懸濁液を細胞ストレーナ(メッシュサイズ=40μm)に通し、続いて、遠心分離することにより、細胞を収集した。細胞を、2×105細胞/mlの密度で、非組織培養物で処理したペトリ皿に播種し、37℃で5%のCO2で培養した。培養培地を、3日目、6日目、及び8日目にリフレッシュし、BMDCを、8日目~12日目に使用した。
BMDC上の活性化マーカーの上方制御
未成熟BMDCを、使用の24時間前に、12ウェルプレートに、1×106細胞/ウェルで播種した。古い培地を、吸引し、24時間37℃で、0.5μg/mLの異なるCpG含有製剤または0.5μg/mLのLPS(陽性対照)と共にインキュベートする前に、BMDCをPBSで1回洗浄した。BMDCを採取し、FACS緩衝液(PBS中1%のBSA)で1回洗浄し、室温で10分間、抗CD16/32と共にインキュベートし、次に、室温で30分間、CD11c、CD40、CD80、CD86、及びMHCクラスIIに対する蛍光プローブ標識抗体で染色した。最終的に、細胞を、FACS緩衝液で2回洗浄し、2μg/mlのDAPI溶液に再懸濁し、フローサイトメトリー(Cyan
5、Beckman Coulter、米国)で分析した。
BMDCによる抗原提示
未成熟BMDCを、使用の24時間前に、12ウェルプレートに、1×106細胞/ウェルで播種した。古い培地を吸引し、BMDCをPBSで1回洗浄した後、異なる時間(2時間、6時間、24時間、及び48時間)、37℃、完全培地中で、0.5μg/mLのCpG及び/または0.5μg/mLの抗原ペプチド含有製剤と共にインキュベートした。BMDCを採取し、FACS緩衝液で1回洗浄し、室温で10分間抗CD16/32と共にインキュベートし、次に、室温で30分間、PEタグ化抗マウスSIINFEKLH-2Kbモノクローナル抗体25-D1.16で染色した。最終的に、細胞を、FACS緩衝液で2回洗浄し、2μg/mlのDAPI溶液に再懸濁し、フローサイトメトリー(Cyan 5、Beckman Coulter、米国)で分析した。
CLSMを用いた、sHDLベースのペプチドワクチンの細胞内送達のイメージング
2mLの完全培地中の1×106細胞のJAWSII細胞を、同じ培地で予め平衡化している35mmのペトリ皿(MatTek)に播種し、一晩を沈殿させた。sHDL自体の細胞内送達プロファイルを知るため、DOPE-Rhodを使用して、sHDLの脂質を標識し、Texas Red(登録商標)-X、スクシンイミジルエステル(Life
Technologies)と共にsHDLをインキュベートすることにより、sHDLの22Aペプチドを標識し、続いて、未反応の染料を除去するために脱塩カラムを通過させた。これらの標識sHDLを、37℃で24時間、JAWSII細胞と共にインキュベートした。インキュベーション後、細胞をPBSで3回洗浄し、30分間37℃で、フェノール及び500nMのLysoTracker(登録商標)Green DND-26(Life Technologies)を含有する無血清培地及び2ug/mLのHoechstと共にインキュベートして、リソソーム及び核をそれぞれ染色し、その後、共焦点顕微鏡(Nikon A1)を使用してイメージングした。抗原ペプチドの細胞内送達プロファイルを知るために、遊離CSSSIINFEK(FITC)L+CpGまたはsHDL-CSSSIINFEK(FITC)L/CpGを、異なる時間(6時間、24時間、及び48時間)、JAWSII細胞と共にインキュベートした。インキュベーション後、細胞をPBSで3回洗浄し、30分間37℃で、フェノール及び50nMのLysoTracker(登録商標)Red DND-99(Life Technologies)を含有する無血清培地及び2ug/mLのHoechstと共にインキュベートして、リソソーム及び核をそれぞれ染色し、その後、共焦点顕微鏡(Nikon A1)を使用してイメージングした。
インビトロでのB3Z T細胞活性化
BMDCを、U底96ウェルプレートに、5×104細胞/ウェルで播種し、一晩成長させた。古い培地を吸引し、BMDCを、PBSで1回洗浄し、その後、37℃で、24時間または48時間、製剤を含有する異なる濃度(0.02、0.1、及び0.5μg/mL)のSIINFEKL及びCpGと共にインキュベートした。インキュベーション後、細胞をPBSで3回注意深く洗浄し、10×104個のB3Z T細胞/ウェルを添加し、10%のFBS、2mMのL-グルタミン、55μMのβ-メルカプトエタノール、1mMのピルベート、ならびに100U/mLのペニシリン及び100μg/mLのストレプトマイシンを補充したRPMI 1640中でさらに24時間共培養した。次に、細胞を遠心分離(1500rcf、7分)によりペレット化した。培地を注意深く吸引し、150μLのCPRG/溶解緩衝液(0.15mMのクロロフェノールレッドβ-D-ガラクトピラノシド(CPRG)、0.1%のTriton-X100、9mMのMgCl2、100uMのメルカプトエタノールを含むPBS)を添加した。プレートを、37℃、暗所で90分間インキュベートし、この後、プレートリーダーを使用して、放出されたクロロフェノールレッドの吸光度を570nmで測定した。
抗原ペプチドのリンパ節排出
sHDL-CSSSIINFEK(FITC)Lを、上記のように調製した。6~8週齢の雌C57BL/6マウスを、Harlan Laboratoriesから購入した。C57BL/6マウスに、フリーCSSSIINFEK(FITC)LまたはsHDL-CSSSIINFEK(FITC)Lを皮下注射した。注射の24時間後、マウスを二酸化炭素吸入により安楽死させ、腋窩リンパ節及び鼠径リンパ節を採取し、IVIS光学イメージングシステム(Caliper Lifesciences)でイメージングした。
インビボワクチン接種及びメラノーマ腫瘍成長の予防及び治療環境における細胞傷害性T細胞応答の分析
C57BL/6マウスに、所定のスケジュールに従って、尾の付け根で皮下注射によりSIINFEKL(15μg/マウス)及びCpG(15μg/マウス)を含有する異なる製剤を免疫した。腫瘍抗原特異的CD8+T細胞のパーセントを、テトラマー染色アッセイで、各ワクチン接種の7日後に測定した。簡単に言うと、100μlの血液を各マウスから採血することになり、血液サンプルを、ACK溶解緩衝液で溶解させ、続いて、遠心分離してペレットを収集し、次に、これらを、FACS緩衝液で1回洗浄し、CD16/32遮断抗体でブロッキングし、室温で30分間、PE標識SIINFEKLテトラマーをインキュベートした。次に、サンプルを、氷上で20分間、抗CD8-APCと共にインキュベートした。細胞を、フローサイトメトリー(Cyan 5、Beckman Coulter、米国)で分析するために、FACS緩衝液で2回洗浄し、2μg/mlのDAPI溶液に再懸濁した。T細胞応答の腫瘍成長に対する影響を検討するために、最後のテトラマー染色の1日後に、右脇腹に20万個のB16.OVA/マウスを皮下注射することにより、マウスに投与した。腫瘍の発達を1日おきにモニターし、腫瘍体積を、次式により計算した:腫瘍体積=長さ×幅2×0.52。sHDLワクチン接種の、確立された腫瘍に対する影響を検討するために、C57BL/6マウスの右脇腹に、0日目に皮下注射により、20万個のB16.OVA/マウスを接種した。4日目及び11日目に、マウスに、腫瘍抗原ペプチド(15μg/マウス)及びCpG(15μg/マウス)を含有する異なる製剤を免疫した。腫瘍抗原特異的CD8+T細胞のパーセントを、上記のようにテトラマー染色アッセイで、10日目及び17日目に測定した。腫瘍堆積を、1日おきにモニターした。
aGC-CD1d提示アッセイ
JAWSII細胞を、12ウェルプレートに20万個/ウェルの密度で播種した。48時間後、2000ng/mLのaGCの異なる製剤を含有する新しい培地と、培地を交換した。製剤との20~24時間のインキュベーション後、トリプシン処理により細胞をFACSチューブに採取し、FACS緩衝液で2回洗浄し、次に、10分間室温で、CD16/32遮断試薬と共にインキュベートした。次に、細胞を、30分間室温で、抗マウスaGC-CD1d-PEと共にインキュベートし、FACS緩衝液で2回洗浄し、フローサイトメトリーのために、DAPIを含有する0.3mLのFACS緩衝液に懸濁した。PCSK9 siRNA充填sHDLの特性決定
sHDLに充填されるPCSK9 siRNA分子の量を定量化するために、種々の濃度のPCSK9 siRNAを、sHDLと共にインキュベートした。遊離形態に対する、sHDLと会合するPCSK9 siRNAの濃度は、ゲル浸透クロマトグラフィー(GPC)を使用して260nmで測定されることになる。
HepG2細胞におけるPCSK9ノックダウン
PCSK9 siRNAの異なる製剤を、48時間、HepG2細胞と共にインキュベートした。インキュベーション後、細胞をPBSで2回洗浄し、細胞溶解物を調製した。PCSK9タンパク質レベルを、ウェスタンブロットアッセイで分析した。
sHDLの生体内分布
sHDLの生体内分布を試験するために、DiD充填sHDLを、C57BL/6マウスに静脈注射した。注射の24時間後に、マウスを、安楽死させ、IVIS光学イメージングシステムを使用して、主要器官(心臓、肝臓、脾臓、肺、及び腎臓)におけるsHDLの分布を分析した。
実施例II.
本実施例は、sHDLに組み込まれたPCSK9 siRNAが、肝臓に効率的に蓄積し、そのカーゴをSR-BI陽性細胞に送達し、HepG2細胞中のPCSK9をノックダウンすることができることを実証する。均質なsHDLナノ粒子の調製のための迅速で安価な凍結乾燥方法を実施した。sHDLの均質性を、透過型電子顕微鏡(TEM)、動的レーザー散乱(DLS)、及びゲル浸透クロマトグラフィー(GPC)で確認した(図1A)。sHDLを蛍光色素DiRで標識し、マウスに静脈内注射し、DiRシグナルの大部分を肝臓で検出し、他の器官では、シグナルをほとんどまたは全く検出しなかった(図1B)。sHDLはまた、蛍光色素DiOを、SR-BI陰性細胞(BHK-ベクター)でなく、SR-BI陽性細胞(BHK-SR-BI)に効率的に送達し、SR-BI陽性細胞による取り込みは、過剰なブランクsHDLにより遮断された(図1C)。さらに、予備データは、コレステロール修飾PCSK9 siRNA(PCSK9 Cho-siRNA)が、sHDLに定量的に取り込むことができることを示した。フリーPCSK9 Cho-siRNAが、コレステロールコンジュゲーションにより誘導されたsiRNAの取り込みの増加に起因して、HepG2細胞のPCSK9をノックダウンすることができるが、PCSK9 siRNA-sHDLは依然として十分に、インビトロでHepG2細胞のPCSK9タンパク質をノックダウンすることができる(図1D~F)。
実施例III.
本実施例は、抗原及びアジュバントのsHDLによる共局在送達が、強力な免疫応答をもたらすことを実証する。図4Aは、抗原及びアジュバント充填sHDLの概略図を示す。MHCクラスI抗原ペプチド(卵白アルブミン由来するCD8+T細胞エピトープペプチドSIINFEKL)を、機能性脂質含有sHDLと共にインキュベートした場合、機能性脂質の消失及び脂質-ペプチドコンジュゲートの出現により見ることができるように、抗原ペプチドを、sHDLの機能性脂質に定量的にコンジュゲートした(図2B)。コレステロール修飾CpG(Cho-CpG)が、sHDLに定量的に組み込まれることも示された(図2C)。1回の一次投与及び2回のブースター投与後、抗原及びCpG充填sHDL(sHDL-Ag/CpG)は、Montanide中の抗原とCpGとの混合物よりも強力な免疫応答を誘発した(CpG+Montanideは、臨床評価を受けている現在最も強力な実験的アジュバントの1つである)(図2D)。
実施例IV.
本実施例は、sHDLが、CD1-dに対する糖脂質リガンドであるα-ガラクトシルセラミドを送達して、ナチュラルキラーT細胞の誘導を活性化することを実証する。
実施例V.
本実施例は、予め形成された高密度リポタンパク質模倣ナノディスクが抗原(Ag)ペプチド及びアジュバントと容易に結合し、リンパ器官へのAg/アジュバントの同時送達を顕著に改善し、樹状細胞上で持続したAg提示を達成する安定な超小型ナノ粒子を産生することができることを実証する。
Burg,S.H.Nat.Rev.Cancer 8,351-360(2008))を参照のこと)、1日後の鼠径dLNにおいて最小のFITCシグナルを有した(例えば、図21aを参照のこと)。対照的に、sHDL-Ag群は、dLNにおいてFITCシグナルの顕著な増加を示し(p<0.01、図21a)、Ag(FITC)及びCy5-タグ化22Aは、dLN内に共局在した(図22)。同様に、2.3nmolのCy5タグ化Cho-CpGのsHDLへの注射は、遊離可溶形態の注射と比較して、LN蓄積を増加させた(p<0.01、図21b)。これらの結果は、sHDLナノディスクが、Ag及びCpGのdLNへの同時送達を促進することを示した。次に、C57BL/6マウスに、15.5nmolのAg及び2.3nmolのCpG(非フルオロフォアタグ化)を免疫し、末梢血単核細胞(PBMC)を、SIINFEKL-MHC-Iテトラマー+CD8α+T細胞の頻度について分析した。遊離Agペプチド(SIINFEKLまたはCSS-SIINFEKL)とCpGとの混合物は、3回目の免疫化後に、1~3%のAg特異的CTLを誘導した(図21c及び21d)。ベンチマークとして、油中水型Montanide中に乳化した等価用量のAg及びCpGを有する動物にもワクチン接種した(例えば、Speiser,D.E.et al.J.Clin.Invest.115,739-746(2005);Fourcade,J.et al.J.Immunother.31,781-791(2008)を参照のこと)。Ag+CpG+Montanideは、プライミング後に、約2%のAg特異的CTLを誘発したが、3回目の免疫化後であっても、さらなるT細胞拡大は観察されず、デポー形成油中水型アジュバントでの反復免疫化後の高アビディティーT細胞の機能不全及び欠損を報告した最近の試験と一致していた(例えば、Rezvani,K.et al.Haematologica 96,432-440(2011);Hailemichael,Y.et al.Nat.Med.19,465-472(2013)を参照のこと)。著しく対照的に、sHDL-Ag/CpG群は、3回目のワクチン接種後に、ピーク頻度の約21%のAg特異的CD8α+T細胞を誘発した(可溶性SIINFEKL+CpGよりも29倍大きく、Ag+CpG+Montanideよりも9倍大きい、P<0.0001、図21c及び21d)。2×105個のB16OVA細胞を投与した場合、sHDL-Ag/CpGを免疫したマウスは、28日までは検出可能な腫瘍塊を有さず、動物の40%が200日を超えて生き残ったが、遊離Agペプチド+CpGまたはAg+CpG+Montanideを免疫したマウスは全て、腫瘍で死亡し、延命効果は最低であった(図21e及び2f)。重要なことに、このような実験を通じて、sHDL-Ag/CpGを複数回免疫した動物において毒性または自己免疫の兆候は観察されなかった。
実施例VI.
本実施例は、実施例Vの材料及び方法に関する。
材料
1,2-ジミリストイル-sn-グリセロ-3-ホスホコリン(DMPC)、1,2-ジオレオイル-sn-グリセロ-3-ホスホエタノールアミン(DOPE)、及びローダミン(RHOD)標識DOPE(DOPE-RHOD)を、Avanti Polar Lipids(アラバマ州アラバスター)から購入した。ApoA1模倣ペプチド(22A)、OVA257-264 SIINFEKL、CSSSIINFEKL、CSSSIINFEK(FITC)L、hgp10025-33KVPRNQDWL、CSSSKVPRNQDWL、及びAdpgk変異体ペプチドASMTNMELMは、GenScript Corp.(ニュージャージー州ピスカタウェイ)により合成された。CSSASMENMELMは、AnaSpec(カリフォルニア州フリーモント)により合成された。オリゴデオキシヌクレオチドTLR9リガンドCpG 1826(5’-tccatgacgttcctgacgtt-3’、小文字は、ホスホロチオエート骨格を表す)、3’末端でコレステロールにより修飾されたCpG1826(Cho-CpG)、及びCy5修飾Cho-CpGは、Integrated DNA Technologies(アイオワ州コーラルビル)により合成された。HPLCグレードのメタノール及びアセトニトリルを、Fisher Scientific(ペンシルベニア州ピッツバーグ)から購入した。ウシ胎児血清(FBS)、ペニシリン-ストレプトマイシン、β-メルカプトエタノール、及びACK溶解緩衝液を、Life Technologies(ニューヨーク州グランドアイランド)から購入した。顆粒球マクロファージコロニー刺激因子(GM-CSF)は、GenScript Corp.(ニュージャージー州ピスカタウェイ)から入手した。抗マウスCD16/32、CD86-PE、CD40-APC、CD62L-PECy7、及びSIINFEKL/H-2Kbに対する25-D1.16 mAb-PEは、eBioscience(カルフォルニア州サンディエゴ)から入手した。抗マウスCD8α-APC、CD44-FITC、TNF-α-FITC、IFN-γ-PE、及びCD11c-PECy7は、BD Bioscience(カルフォルニア州サンノゼ)から入手した。Tetramer H-2Kb-SIINFEKL-PE及びTetramer H-2Db-KVPRNQDWL-PEを、Beckman Coulter(カルフォルニア州ブレア)から購入した。テトラマー/H-2Db-ASMTNMELM-PEは、NIH Tetramer Core Facility(ジョージア州アトランタ)により厚意で提供された。B3Z CD8α+T細胞ハイブリドーマをN.Shastri博士(University of California, Berkeley)から、B16OVAをKenneth Rock博士(University of Massachusetts、マサチューセッツ州アマースト)から;MC-38細胞を、Weiping Zou博士(University of Michigan、ミシガン州アナーバー)から入手した。
方法
DOPE-PDPの合成及び特性決定
ジオレオイル-sn-グリセロ-3-ホスホエタノールアミン-N-[3-(2-ピリジルジチオ)プロピオネート](DOPE-PDP)を、わずかに改変して以前に報告されたように合成した(例えば、Kuai,R.,et al.Mol.Pharm.7,1816-1826(2010)を参照のこと)。要約すると、DOPE、SPDP(スクシンイミジル3-(2-ピリジルジチオ)プロピオネート)及びトリエチルアミン(1:1:1.5モル比)をクロロホルムに溶解した。混合物を暗所で5時間反応させた。反応の進行は、展開溶媒として次の混合物を使用した薄層クロマトグラフィー(TLC)でモニターした:クロロホルム/メタノール/水=65/25/4(体積比)。TLCが、出発物質の消失及びより速いランニングスポットの出現を示した後、反応混合物をロータリーエバポレーションで乾燥させ、シリカゲルカラムで精製した。
抗原ペプチド及びCpGが同時充填されたsHDLの合成
DMPCとDOPE-PDP(モル比=96:4)をクロロホルムに溶解させた。混合物を窒素気流で乾燥させ、少なくとも1時間真空下に定置した。得られた脂質フィルムを、10mMのリン酸ナトリウム緩衝液(0.3117g/LのNaH2PO4・H2O及び2.0747g/LのNa2HPO4・7H2O、pH7.4)で水和し、10分間、バスソニケーター中で超音波処理し、続いて、さらに2.5分間プローブ音波処理した。エンドトキシンフリー水に溶解させたApoA1模倣ペプチド22Aは、上記混合物(22A:脂質=1:7.5、モル比)に添加し、次に、これを、3分間加熱して(50℃)、3分間冷却(氷水)し、これを合計3サイクル行い、sHDLを得た。
ペプチド/CpG充填sHDL製剤の特性決定
sHDL製剤を、PBSで0.5mg/mLの22Aに希釈し、粒径を、動的光散乱(DLS、Zetasizer Nano ZSP、Malvern、英国)で測定した。元のサンプルを適切に希釈した後、透過型電子顕微鏡(TEM)により、sHDLのモルホロジーを観察した。要約すると、3μLのサンプル溶液を、カーボンフィルムで被覆された400メッシュ銅グリッド(Electron Microscopy Sciences)上に堆積させ、1分間乾燥させた。次に、サンプルを、1%酢酸ウラニル溶液5滴を用いて陰性染色し、グリッド上の過剰な溶液を拭い、グリッドをTEM観察の前に乾燥させた。全てのイメージを、AMT XR-60デジタルカメラ(Advanced Microscopy Techniques Corp.、マサチューセッツ州ウォーバーン)が装着されたJEM 1200EX電子顕微鏡(JEOL USA、マサチューセッツ州ウォーバーン)で取得した。
BMDCの調製
BMDCを、以前に記載したように調製した(例えば、Lutz,M.B.,et al.J.Immunol.Methods 223,77-92(1999)を参照のこと)。要約すると、大腿骨及び脛骨をC57BL/6マウスから無菌採取し、BMDC培地(10%のFBS、100U/mLのペニシリン、100μg/mlのストレプトマイシン、50μMのβ-メルカプトエタノール、及び20ng/mlのGM-CSFを補充したRPMI 1640)を装填した5mLの注射器(26G針)を使用して、骨髄をペトリ皿に洗い流した。細胞懸濁液を細胞ストレーナ(メッシュサイズ=40μm)に通し、続いて、遠心分離することにより、細胞を収集した。細胞を、2×105細胞/mlの密度で、非組織培養物で処理したペトリ皿に播種し、37℃、5%のCO2で培養した。培地を、3日目、6日目、8日目、及び10日目にリフレッシュし、BMDCを、8~12日目の次のアッセイに使用した。
BMDCの活性化
未成熟BMDCを、12ウェルプレートに、1×106細胞/ウェルで播種した。24時間後、BMDCをPBSで1回洗浄し、24時間37℃、5%CO2で、異なる処方の75nMのCpGまたは0.5μg/mLのLPS(陽性対照)と共にインキュベートした。BMDCを採取し、FACS緩衝液(PBS中1%BSA)で洗浄し、室温で少なくとも10分間、抗CD16/32と共にインキュベートし、次に、室温で30分間、CD11c、CD40、CD80、及びCD86に対するフルオロフォア標識抗体で染色した。最終的に、細胞を、FACS緩衝液で2回洗浄し、2μg/mlのDAPI溶液に再懸濁し、フローサイトメトリー(Cyan 5、Beckman Coulter、米国)で分析した。
BMDC上の抗原提示
未成熟BMDCを、使用の24時間前に、12ウェルプレートに、1×106細胞/ウェルで播種した。BMDCを、PBSで洗浄し、完全培地中で異なる時間(2時間、6時間、24時間、及び48時間)、種々の処方の75nMのCpG及び/または500nMの抗原ペプチドと共にインキュベートした。次に、BMDCを採取し、FACS緩衝液で洗浄し、室温で少なくとも10分間、抗CD16/32と共にインキュベートし、室温で30分間、PEコンジュゲート抗マウスSIINFEKL/H-2KB mAb 25-D1.16で染色した。次に、細胞を洗浄し、2μg/mlのDAPI溶液に再懸濁し、フローサイトメトリー(Cyan 5、Beckman Coulter、米国)で分析した。
sHDLの細胞内輸送の共焦点顕微鏡イメージング
JAWSII細胞(ATCC、バージニア州マナッサス)を、完全細胞培地で予め平衡化されている35mmのペトリ皿(MatTek Corp.、マサチューセッツ州アシュランド)に1×106細胞で播種し、一晩培養した。抗原ペプチドの細胞内送達プロファイルを調査するために、JAWSII細胞を、異なる時間(6時間、24時間、及び48時間)、遊離CSSSIINFEK(FITC)LとCpGまたはsHDL-CSSSIINFEK(FITC)L/CpGとの物理的混合物と共にインキュベートした。次に、細胞をPBSで3回洗浄し、フェノール/無血清培地中で、50nMのLysoTracker(登録商標)Red DND-99(Invitrogen)及び2μg/mLのHoechstと共に30分間37℃でインキュベートして、それぞれ、リソソーム及び核を染色した。並行して、sHDLの構造構成要素の細胞内送達プロファイルを試験するために、0.5モル%のDOPE-Rhodを最初の脂質フィルムに添加することにより、sHDLの脂質層をDOPE-Rhod共に組み込む一方、予め形成したsHDLをTexas Red(登録商標)-Xスクシンイミジルエステル(Life Technologies)と共にインキュベートし、Texas Red標識sHDLを脱塩カラムに通過させて、未反応染料を除去することにより、sHDLの22Aペプチドを標識した。得られたフルオロフォアタグ化sHDL製剤を、37℃、5%CO2で、JAWSII細胞と共にインキュベートした。24時間のインキュベーション後、細胞をPBSで3回洗浄し、次に、フェノール/無血清培地中で、500nMのLysoTracker(登録商標)Green DND-26(Invitrogen)及び2μg/mLのHoechstと共に30分間37℃でインキュベートして、それぞれ、リソソーム及び核を染色した。次に、共焦点顕微鏡(Nikon A1)を使用して、JAWSII細胞をイメージングした。
B3Z CD8+Tハイブリドーマ細胞のsHDLを用いた活性化
BMDCを、U底96ウェルプレートに5×104細胞/ウェルで播種した。一晩培養後、BMDCをPBSで洗浄し、24時間または48時間37℃で、異なる処方のSIINFEKL(20、100、及び500nM)ならびにCpG(3、15、及び75nM)と共にインキュベートした。次に、細胞を、PBSで3回注意深く洗浄し、105個のB3Z CD8+Tハイブリドーマ細胞/ウェルを、10%のFBS、2mMのL-グルタミン、55μMのβ-メルカプトエタノール、1mMのピルベート、ならびに100U/mLのペニシリン及び100μg/mLのストレプトマイシンを補充したRPMI 1640に添加した。24時間のインキュベーション後、細胞を遠心分離でペレット化し(1500rcf、7分)、培地を注意深く吸引し、150μLのCPRG/溶解緩衝液(0.15mMのクロロフェノールレッドβ-D-ガラクトピラノシド(CPRG)、0.1%のTriton-X100、9mMのMgCl2、100uMのメルカプトエタノールのPBS)を添加した。プレートを、37℃、暗所で90分間、インキュベートし、この後、マイクロプレートリーダーを使用して、放出されたクロロフェノールレッドの吸光度を、570nmで測定した。
インビボ免疫試験
動物は、連邦、州、及びローカルのガイドラインに従いケアした。動物に実施した全ての試験は、University of Michigan,Ann ArborでのUniversity Committee on Use and Care of Animals(UCUCA)に従い、承認された。6~8週齢の雌C57BL/6マウス(Harlan Laboratories)に、抗原ペプチド(15.5nmol/マウス)及びCpG(2.3nmol/マウス)を含有する100μlの容量の異なる製剤を、示された時点で尾の付け根に皮下注射することにより、免疫した。一部の試験では、Montanide中で乳化された抗原ペプチド及びCpGは、陽性対照として役立った(例えば、Speiser,D.E.,et al.J.Clin.Invest.115,739-746(2005);Fourcade,J.,et al.J.Immunother.31,781-791(2008);Karbach,J.,et al.Int.J.Cancer 126,909-918(2010)を参照のこと)。要約すると、抗原ペプチド(155nmol)及びCpG(23nmol)の0.5mLのPBSを、混合物が均質になるまで、0.5mLのMontanide中で完全に乳化させた。
ペプチド-MHCテトラマーアッセイ
免疫化マウスを、以前に記載したように(例えば、Ochyl,L.J.& Moon,J.J.J.Vis.Exp.e52771(2015)を参照のこと)、テトラマー染色アッセイを使用して、末梢血単核細胞(PBMC)の中の腫瘍抗原特異的CD8α+T細胞のパーセンテージについて分析した。簡単に言うと、100μlの血液を、顎下出血により示された時点で各マウスから採血し、赤血球をACK溶解緩衝液で溶解させた。次に、PBMCをFACS緩衝液で洗浄し、抗CD16/32抗体でブロックし、30分間室温で、PEでタグ化したペプチド-MHCテトラマー(例えば、H-2Kb拘束性SIINFEKL、H-2Db拘束性KVPRNQDWL、またはH-2Db拘束性ASMTNMELM)と共にインキュベートした。次に、サンプルを、20分間氷上で抗CD8α-APCと共にインキュベートした。細胞を、フローサイトメトリー(Cyan 5、Beckman Coulter、米国)で分析するために、FACS緩衝液で2回洗浄し、2μg/mlのDAPI溶液に再懸濁した。
ELISPOT及び細胞内サイトカイン染色アッセイ
ELISPOTアッセイのために、免疫化マウス由来の脾臓を無菌採取し、各マウスのための単一細胞懸濁液に加工し、IFN-γコーティングAb(R&D Systems)と共に一晩プレインキュベートした96ウェルPVDFプレート(EMD Millipore)に1ウェル毎に3×105個の脾細胞で播種した。脾細胞を、24時間、抗原ペプチド(2.5μg/ml)または対照と共にインキュベートした。ビオチン化二次Ab、ストレプトアビジン-アルカリホスファターゼ(Sigma Chemical)、及びNBT/BCIP基質(Surmodics)を用いた連続インキュベーションを使用して、アッセイを完了した。AID iSpot Reader(Autoimmun
Diagnostika GmbH、独国)を使用して、発現したスポットの数を数えた。細胞内サイトカイン染色(ICS)アッセイでは、ワクチン接種したマウスから収集した100~150μL末梢血を、ACK溶解緩衝液で溶解し、PBSで洗浄し、96ウェルU底プレート中の50μLのT細胞培地(10%のFBS、2mMのL-グルタミン、55μMのβ-メルカプトエタノール、1mMのピルベート、ならびに100U/mLのペニシリン及び100μg/mLストレプトマイシン、HEPES、ならびに非必須アミノ酸を補充したRPMI 1640)に、約1000万細胞/mLで播種した。細胞に、10μg/mLの抗原ペプチドを6時間パルスし、タンパク質輸送阻害薬ブレフェルジンA(BD Biosciences)を最後の4時間のインキュベーション中に添加した。次に、細胞を氷冷FACS緩衝液(PBS中1%のBSA)で2回洗浄し、続いて、氷上で、少なくとも10分間、抗CD16/32と共に、かつ氷上で、20分間、抗CD8αと共にインキュベートした。次に、細胞を氷上で20分間固定/透過処理し、次に、氷上で30分間、抗IFN-γ-PE及び抗TNF-α-FITCで染色した。広範に洗浄した後、細胞をフローサイトメトリーで分析した。
MC-38細胞におけるネオエピトープ(Adpgk)のcDNAシークエンシング
全RNAを、製造者の使用説明書に従って、RNeasy(登録商標)mini Kit(QIAGEN)でMC-38細胞から抽出した。1μgの全RNAを使用して、第1鎖cDNAを、SuperScript(商標)III First-Strand Synthesis SuperMix Kit(Invitrogen)で合成した。次の2セットの配列特異的プライマーを使用して、長さが250bp及び485bpのAdpgk cDNAを、選択的に増幅した。プライマー1:TGCCAACCGCTTCATCTTCT(フォワードプライマー)及びGGTAGACCAGCGTGTGGAAA(リバースプライマー)。プライマー2:CTCCAACGGGGCCATGAATA(フォワードプライマー)及びCGTGGGAAAGACCTGCTGAT(リバースプライマー)。SuperScript One Step RT-PCR System(Invitrogen)を使用して、増幅を実施した。最終cDNA産物を、臭化エチジウムを含む1.5%のアガロースゲルで可視化し、PureLink(登録商標)Quick Gel Extraction及びPCR Purification Combo Kit(Invitrogen)を使用して、AdpgkのcDNAバンドを切断及び精製した。精製されたcDNAを、University of Michigan DNA Sequencing Coreで、Sangerシークエンシング法(例えば、Sanger,F.,Nicklen,S.& Coulson,A.R.DNA sequencing with chain-terminating inhibitors.Proc.Natl.Acad.Sci.U.S.A.74,5463-5467(1977)を参照のこと)によりシークエンスした。
実施例VII.
本実施例は、sHDL、リポソーム、及び金ナノ粒子を含む他のナノ粒子を使用したネオアンチゲンワクチン接種(図29)、ならびに複数のネオアンチゲンペプチドを使用した多価ネオアンチゲンワクチン接種の生成(図28)について記載する。
多価ネオアンチゲンが充填されたsHDLの調製
ナノディスクベースの多価ペプチドワクチンを調製するために、N末端でCSSリンカーにより修飾された複数のネオアンチゲンペプチド(M30及びM27)を、室温で3時間、ジメチルホルムアミド中でDOPE-PDPにコンジュゲートし、続いて、10×水で希釈し、凍結乾燥して、脂質-ペプチドコンジュゲートを得た。コンジュゲートを、酢酸中のDMPC及び22Aと混合し、凍結乾燥した。次に、得られた粉末を、3分間加熱し(50℃)、3分間冷却し(氷水)、これを合計3サイクル行い、異なるネオアンチゲンが充填されたsHDL(sHDL-M30/M27)を得た。あるいは、コンジュゲートを、DMSOに溶解し、予め形成されたsHDLと共にインキュベートして、異なるネオアンチゲンが充填されたsHDL(sHDL-M30/M27)を得た。脱塩カラムを通過させることにより、あらゆる取り込まれていないネオアンチゲンペプチドを除去した。充填効率をHPLCで分析した。コレステロール-CpGを、室温で30分間上記sHDLと共にインキュベートして、ナノディスクベースの多価ペプチドワクチン(sHDL-M30/M27/CpG)を得た。
ネオアンチゲンが充填されたリポソームの調製
リポソームベースのネオアンチゲンワクチンを調製するために、DMPC及びDOPE-PDP(モル比=92:8)をクロロホルムに溶解した。混合物を、窒素気流で乾燥させ、真空下に少なくとも1時間定置した。得られた脂質フィルムを、10mMのリン酸ナトリウム緩衝液(0.3117g/LのNaH2PO4.H2O及び2.0747g/LのNa2HPO4.7H2O、pH7.4)中で水和し、10分間、バスソニケーター中で超音波処理し、続いて、さらに2.5分間プローブ音波処理して、リポソームを得た。CSS修飾AdpgkペプチドをPDP提示リポソームと共にインキュベートし、続いて、コンジュゲートされないペプチドの脱塩カラムに基づく分離を行った後、ネオアンチゲンペプチドAdpgkを、リポソームにコンジュゲートした。コンジュゲーション効率をHPLCで分析した。コレステロール-CpGを、室温で30分間上記リポソームと共にインキュベートして、リポソームベースのネオアンチゲンペプチドワクチン(lip-Adpgk/CpG)を得た。
スパイク状金ナノ粒子ベースのネオアンチゲンペプチドワクチンの調製
スパイク状金ナノ粒子(AuNP)を得るために、シトラート金ナノ粒子を、まず、HAuCl4水溶液をクエン酸ナトリウムと沸騰させることにより調製した。それらを、激しく撹拌しながら、室温で、HAuCl4、HCl、AgNO3、及びアスコルビン酸と共に順次添加して、種核成長法によりAuNPを形成した。合成したままのAuNPを精製し、0.01%のSDSを用いた遠心分離で濃縮した。ネオアンチゲンペプチドのAuNP上でのチオール媒介製表面装飾、続く、静電複合化によるpolyIC及びCpG層の充填により、AuNPベースのペプチドワクチンを調製した。要約すると、AuNPをCSS修飾されたネオアンチゲンペプチドであるCSS-ASMTNMELMと共に一晩インキュベートすることにより、ペプチドワクチンを、AuNPに表面コンジュゲートさせた。あらゆる未反応ペプチドを、遠心分離によりAuNPコンジュゲートから除去した。静電相互作用により、polyIC及びCpGを充填するために、ポリエチレングリコール(平均Mn6,000)修飾ポリエチレンイミン(分枝状、平均Mw約25,000)(PEG-PEI)を用いた。ペプチドコンジュゲートAuNPsを、10分間、PEG-PEIと混合し、遠心分離により過剰なPEG-PEGから精製し、10mMのNaCl中のpolyIC及びCpG混合溶液に添加した。5分後、混合物を10mMのNaClのPEG-PEI溶液に移し、塩濃度を、5分毎に50mMの増分で、150mMのNaClまで段階的に増加させた。最終的に、粗混合物溶液を、0.01%のtween20を用いて遠心分離して、あらゆる結合していないpolyIC及びCpGを除去した。
細胞内サイトカイン染色
0日目、7日目、及び14日目に、C57BL/6マウスに、ナノディスクベースの多価ネオアンチゲンペプチドワクチン(sHDL-M30/M27/CpG)をワクチン接種した。最後のワクチン接種の7日後、ワクチン接種したマウスから収集した100~150μLの末梢血を、ACK溶解緩衝液で溶解し、PBSで洗浄し、96ウェルU底プレート中の50μLのT細胞培地(10%のFBS、2mMのL-グルタミン、55μMのβ-メルカプトエタノール、1mMのピルベート、ならびに100U/mLのペニシリン及び100μg/mLストレプトマイシン、HEPES、ならびに非必須アミノ酸を補充したRPMI 1640)に、約1000万細胞/mLで播種した。細胞を、50000のBMDC/ウェルと共培養し、細胞に、6時間、20μg/mLのM30またはM27ペプチドをパルスし、タンパク質輸送阻害薬ブレフェルジンA(BD Biosciences)を、最後の4時間のインキュベーション中に添加した。次に、細胞を氷冷FACS緩衝液(PBS中1%のBSA)で2回洗浄し、続いて、氷上で、少なくとも10分間、抗CD16/32と共に、かつ氷上で、20分間、抗CD8α及び抗CD4と共にインキュベートした。次に、細胞を氷上で20分間固定/透過処理し、次に、氷上で30分間、抗IFN-γ-PEで染色した。広範に洗浄した後、細胞をフローサイトメトリーで分析した。図28に示す結果は、sHDL-M30/M27/CpGが、ネオアンチゲンM30に対する高頻度のCD4+T細胞(図28A)及びネオアンチゲンM27に対するCD8+T細胞(図28B)を生成したことを示している。
治療学的試験
治療腫瘍ワクチン接種試験では、C57BL/6マウスに、0日目の皮下注射により、右脇腹に、腫瘍細胞(マウス1匹につき1×105個のMC38細胞)を接種した。マウスに、リポソーム形態または可溶性形態のいずれかで製剤化した15.5nmolのASMTNMELM及び2.3nmolのCpG(または15μgのpolyIC/マウス)を、10及び17日目にワクチン接種した。AuNPを免疫したマウス群について、Adpgk及びアジュバントにより修飾したAuNPの腫瘍内投与を、マウス1匹につき、12nmolのASMTNMELM、5.2nmolのCpG、及び83μgのpolyICと共に、10日目(レーザーありの群及びなしの群の両方)及び16日目(レーザーなしの群のみ)に実施した。808nmのCWダイオードレーザーを使用して、レーザーを、1.2W/cm2で5分間、腫瘍組織に直接照射した。
参照による組み込み
本明細書で参照された各特許文献及び科学論文の開示全体は、あらゆる目的のために参照により組み込まれる。
均等物
本発明は、その趣旨または本質的な特徴から逸脱することなく、他の特定の形態で具体化されてもよい。それ故、上述の実施形態は、本明細書に記載の本発明を限定するものよりもむしろ、あらゆる点で例示的なものであると考えられるべきである。したがって、本発明の範囲は、上述の明細書よりはむしろ添付の特許請求の範囲により示され、特許請求の範囲の均等物の意味及び範囲内に入る全ての変更がその中に含まれるものとする。
Claims (9)
- sHDLナノ粒子を含む組成物であって、
前記sHDLナノ粒子は、
(i)1,2-ジミリストイル-sn-グリセロ-3-ホスホコリン(DMPC)およびジパルミトイルホスファチジルコリン(DPPC)から選択されるリン脂質、
(ii)チオール反応性リン脂質、および、
(iii)配列PVLDLFRELLNELLEALKQKLK(配列番号4)を有するアポリポタンパク質模倣物、を含む、組成物。 - 1つ以上の抗原をさらに含み、
前記1つ以上の抗原は前記ナノ粒子の外面上の前記チオール反応性リン脂質と複合化されている、請求項1に記載の組成物。 - 1つ以上の核酸をさらに含み、
前記1つ以上の核酸は前記ナノ粒子の外面上の前記チオール反応性リン脂質と複合化されている、請求項1に記載の組成物。 - 前記1つ以上の核酸がsiRNAである、請求項3に記載の組成物。
- アジュバントをさらに含む、請求項1に記載の組成物。
- 前記アジュバントが、CpG免疫刺激オリゴヌクレオチド、polyIC、poly-ICLC、イミキモド、レシキモド、ガルジコモド、イミダゾキノリンおよびテルラトリモドからなる群から選択される、請求項5に記載の組成物。
- 前記リン脂質がDMPCである、請求項1に記載の組成物。
- 前記リン脂質がDPPCである、請求項1に記載の組成物。
- 前記チオール反応性リン脂質が、ジオレオイル-sn-グリセロ-3-ホスホエタノールアミン-N-[3-(2-ピリジルジチオ)プロピオネート](DOPE-PDP)、1,2-ジ(9Z-オクタデセノイル)-sn-グリセロ-3-ホスホエタノールアミン-N-[4-(p-マレイミドフェニル)ブチルアミド]、1,2-ジヘキサデカノイル-sn-グリセロ-3-ホスホエタノールアミン-N-[4-(p-マレイミドフェニル)ブチルアミド]、1,2-ジヘキサデカノイル-sn-グリセロ-3-ホスホエタノールアミン-N-[4-(p-マレイミドメチル)シクロヘキサン-カルボキサミド]、および、1,2-ジ-(9Z-オクタデセノイル)-sn-グリセロ-3-ホスホエタノールアミン-N-[4-(p-マレイミドメチル)シクロヘキサン-カルボキサミド]から選択される、請求項1に記載の組成物。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2023031818A JP2023071864A (ja) | 2015-03-25 | 2023-03-02 | 生体高分子薬を送達するための組成物及び方法 |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562138186P | 2015-03-25 | 2015-03-25 | |
US62/138,186 | 2015-03-25 | ||
US201562248908P | 2015-10-30 | 2015-10-30 | |
US62/248,908 | 2015-10-30 | ||
JP2020002708A JP6933403B2 (ja) | 2015-03-25 | 2020-01-10 | 生体高分子薬を送達するための組成物及び方法 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020002708A Division JP6933403B2 (ja) | 2015-03-25 | 2020-01-10 | 生体高分子薬を送達するための組成物及び方法 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023031818A Division JP2023071864A (ja) | 2015-03-25 | 2023-03-02 | 生体高分子薬を送達するための組成物及び方法 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021181484A JP2021181484A (ja) | 2021-11-25 |
JP7244124B2 true JP7244124B2 (ja) | 2023-03-22 |
Family
ID=56978645
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017550227A Pending JP2018516847A (ja) | 2015-03-25 | 2016-03-25 | 生体高分子薬を送達するための組成物及び方法 |
JP2020002708A Active JP6933403B2 (ja) | 2015-03-25 | 2020-01-10 | 生体高分子薬を送達するための組成物及び方法 |
JP2021131737A Active JP7244124B2 (ja) | 2015-03-25 | 2021-08-12 | 生体高分子薬を送達するための組成物及び方法 |
JP2023031818A Pending JP2023071864A (ja) | 2015-03-25 | 2023-03-02 | 生体高分子薬を送達するための組成物及び方法 |
Family Applications Before (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017550227A Pending JP2018516847A (ja) | 2015-03-25 | 2016-03-25 | 生体高分子薬を送達するための組成物及び方法 |
JP2020002708A Active JP6933403B2 (ja) | 2015-03-25 | 2020-01-10 | 生体高分子薬を送達するための組成物及び方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2023031818A Pending JP2023071864A (ja) | 2015-03-25 | 2023-03-02 | 生体高分子薬を送達するための組成物及び方法 |
Country Status (8)
Country | Link |
---|---|
US (3) | US11219673B2 (ja) |
EP (1) | EP3273944A4 (ja) |
JP (4) | JP2018516847A (ja) |
AU (3) | AU2016238290B9 (ja) |
BR (1) | BR112017020491A2 (ja) |
CA (1) | CA2979712C (ja) |
MX (2) | MX2017012131A (ja) |
WO (1) | WO2016154544A1 (ja) |
Families Citing this family (35)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EA201692458A1 (ru) | 2014-05-28 | 2017-06-30 | Агенус Инк. | Анти-gitr антитела и способы их применения |
CA2979712C (en) * | 2015-03-25 | 2024-01-23 | The Regents Of The University Of Michigan | Nanoparticle compositions for delivery of biomacromolecules |
CA2984794A1 (en) | 2015-05-07 | 2016-11-10 | Agenus Inc. | Anti-ox40 antibodies and methods of use thereof |
EP3383430A4 (en) | 2015-12-02 | 2019-12-18 | Agenus Inc. | ANTIBODIES AND METHOD FOR USE THEREOF |
TWI794171B (zh) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Hdac抑制劑與pd-l1抑制劑之組合治療 |
TWI808055B (zh) | 2016-05-11 | 2023-07-11 | 美商滬亞生物國際有限公司 | Hdac 抑制劑與 pd-1 抑制劑之組合治療 |
TWI781934B (zh) | 2016-05-27 | 2022-11-01 | 美商艾吉納斯公司 | 抗-tim-3抗體及其使用方法 |
US20210106538A1 (en) * | 2016-06-20 | 2021-04-15 | The Regents Of The University Of Michigan | Compositions and methods for delivery of biomacromolecule agents |
EP3538152A4 (en) | 2016-11-09 | 2020-09-30 | Agenus Inc. | ANTI-OX40 ANTIBODIES, ANTI-GITR ANTIBODIES AND METHOD OF USING THEREOF |
AU2018214556A1 (en) | 2017-02-01 | 2019-08-15 | Modernatx, Inc. | Immunomodulatory therapeutic mRNA compositions encoding activating oncogene mutation peptides |
MX2019012223A (es) | 2017-04-13 | 2019-12-09 | Agenus Inc | Anticuerpos anti-cd137 y metodos de uso de los mismos. |
US20200138727A1 (en) * | 2017-04-21 | 2020-05-07 | University Of North Texas Health Science Center | Enhanced therapeutic agent and nucleic acid delivery via hdl or reconstituted hdl nanoparticles |
HRP20230941T1 (hr) | 2017-05-01 | 2023-11-24 | Agenus Inc. | Anti-tigit antitijela i postupci njihove primjene |
CA3082830A1 (en) * | 2017-11-21 | 2019-05-31 | Icahn School Of Medicine At Mount Sinai | Promoting trained immunity with therapeutic nanobiologic compositions |
WO2019226875A1 (en) * | 2018-05-23 | 2019-11-28 | Mayo Foundation For Medical Education And Research | Microencapsulated modified polynucleotide compositions and methods |
KR20210044212A (ko) * | 2018-07-12 | 2021-04-22 | 더 리젠츠 오브 더 유니버시티 오브 미시간 | 면역 반응을 조절할 수 있는 금속 함유 제형의 조성물 및 방법 |
CN112702994A (zh) | 2018-09-18 | 2021-04-23 | 根特大学 | 治疗性纳米颗粒及其使用方法 |
WO2020136657A1 (en) * | 2018-12-28 | 2020-07-02 | Ramot At Tel-Aviv University Ltd. | Polymeric nanovaccines and uses thereof |
WO2020201568A1 (en) * | 2019-04-03 | 2020-10-08 | Targimmune Therapeutics Ag | Immunotherapy for the treatment of cancer |
US20220249389A1 (en) | 2019-07-12 | 2022-08-11 | Oregon Health & Science University | Immunotherapeutic constructs and methods of their use |
MX2022000541A (es) | 2019-07-12 | 2022-04-18 | Univ Oregon Health & Science | Construcciones terapeuticas para la administracion conjunta de un inhibidor de la quinasa mitotica y un inhibidor de puntos de control inmunitario. |
MX2022000752A (es) * | 2019-07-19 | 2022-03-25 | Univ Michigan Regents | Composiciones y metodos para tratar trastornos autoinmunes. |
CN116322779A (zh) * | 2020-09-10 | 2023-06-23 | 联合免疫股份有限公司 | 复合体 |
CN112791067A (zh) * | 2020-12-07 | 2021-05-14 | 江苏中慧元通生物科技有限公司 | 一种用于核酸疫苗递载的脂质体-聚合物杂化纳米颗粒 |
WO2022125878A1 (en) * | 2020-12-11 | 2022-06-16 | The Regents Of The University Of Michigan | Compositions and methods for preventing, attenuating, and treating medical conditions with shdl nanoparticles |
MX2023011004A (es) | 2021-03-19 | 2024-01-08 | Trained Therapeutix Discovery Inc | Compuestos para regular la inmunidad entrenada y métodos para usarlos. |
AR125753A1 (es) | 2021-05-04 | 2023-08-09 | Agenus Inc | Anticuerpos anti-tigit, anticuerpos anti-cd96 y métodos de uso de estos |
KR20230068047A (ko) * | 2021-11-10 | 2023-05-17 | 주식회사 에스엠엘바이오팜 | 트레할로즈 유도체 및 신규 구조 유지 화합물을 포함하는 핵산 의약품 전달용 지질나노입자의 약학 조성물 |
WO2023114820A2 (en) * | 2021-12-14 | 2023-06-22 | Board Of Regents Of The University Of Nebraska | Compositions and methods for modular vaccines |
WO2023141562A1 (en) * | 2022-01-20 | 2023-07-27 | Emory University | Phosphate membrane nanodiscs conjugated to therapeutic agents and medical uses thereof |
WO2023164476A2 (en) * | 2022-02-22 | 2023-08-31 | The Regents Of The University Of Michigan | Compositions and methods for treating autoimmune disorders |
WO2023209103A1 (en) * | 2022-04-29 | 2023-11-02 | Universiteit Gent | Prevention and treatment of infections with intracellular bacteria |
WO2023215549A1 (en) * | 2022-05-05 | 2023-11-09 | Case Western Reserve University | Immunostimulatory nanoparticle |
CN118045169A (zh) * | 2022-11-10 | 2024-05-17 | 中国科学院化学研究所 | 脂质-带电分子偶联物、可吸入式脂质纳米颗粒及其制备方法和应用 |
CN116555346B (zh) * | 2023-07-05 | 2023-09-01 | 中山大学 | 一种采用碳纳米管基因载体递送系统促进草鱼生长的方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002500165A (ja) | 1997-12-31 | 2002-01-08 | オラソマル テクノロジーズ,インコーポレーテッド | 新規の重合性の脂肪酸、リン脂質、及びそれから得られた重合リポソーム |
JP2011528371A (ja) | 2008-07-15 | 2011-11-17 | ノバルティス アーゲー | 免疫原性の両親媒性ペプチド組成物 |
JP2013540106A (ja) | 2010-08-30 | 2013-10-31 | エフ.ホフマン−ラ ロシュ アーゲー | テトラネクチン−アポリポタンパク質a−i、それを含有する脂質粒子及びその使用 |
WO2014096179A1 (en) | 2012-12-19 | 2014-06-26 | Novo Nordisk A/S | Novel glp-1 receptor agonists with cholesterol efflux activity |
Family Cites Families (74)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU564876B2 (en) | 1982-03-29 | 1987-08-27 | Liposome Company, Inc., The | Stable plurilamellar vesicles |
US4588585A (en) | 1982-10-19 | 1986-05-13 | Cetus Corporation | Human recombinant cysteine depleted interferon-β muteins |
GB8311018D0 (en) | 1983-04-22 | 1983-05-25 | Amersham Int Plc | Detecting mutations in dna |
FR2650840B1 (fr) | 1989-08-11 | 1991-11-29 | Bertin & Cie | Procede rapide de detection et/ou d'identification d'une seule base sur une sequence d'acide nucleique, et ses applications |
US5318529A (en) | 1989-09-06 | 1994-06-07 | Boston Scientific Corporation | Angioplasty balloon catheter and adaptor |
US5843089A (en) | 1990-12-28 | 1998-12-01 | Boston Scientific Corporation | Stent lining |
US5674192A (en) | 1990-12-28 | 1997-10-07 | Boston Scientific Corporation | Drug delivery |
US6004744A (en) | 1991-03-05 | 1999-12-21 | Molecular Tool, Inc. | Method for determining nucleotide identity through extension of immobilized primer |
US5876445A (en) | 1991-10-09 | 1999-03-02 | Boston Scientific Corporation | Medical stents for body lumens exhibiting peristaltic motion |
US5354308A (en) | 1992-05-01 | 1994-10-11 | Beth Israel Hospital Association | Metal wire stent |
US5913894A (en) | 1994-12-05 | 1999-06-22 | Meadox Medicals, Inc. | Solid woven tubular prosthesis |
DE69429670T2 (de) | 1993-08-23 | 2002-08-22 | Boston Scientific Corp., Natick | Verbesserter ballonkatheter |
US5609627A (en) | 1994-02-09 | 1997-03-11 | Boston Scientific Technology, Inc. | Method for delivering a bifurcated endoluminal prosthesis |
US5733303A (en) | 1994-03-17 | 1998-03-31 | Medinol Ltd. | Flexible expandable stent |
EP0858298A4 (en) | 1994-04-29 | 1999-04-07 | Boston Scient Corp | MEDICAL STENT PROSTHESIS AND METHOD FOR THE PRODUCTION |
US5857998A (en) | 1994-06-30 | 1999-01-12 | Boston Scientific Corporation | Stent and therapeutic delivery system |
US5620417A (en) | 1994-07-07 | 1997-04-15 | Cardiovascular Imaging Systems Incorporated | Rapid exchange delivery catheter |
US5755722A (en) | 1994-12-22 | 1998-05-26 | Boston Scientific Corporation | Stent placement device with medication dispenser and method |
EP0831753B1 (en) | 1995-06-01 | 2005-12-28 | Meadox Medicals, Inc. | Implantable intraluminal prosthesis |
US5849589A (en) | 1996-03-11 | 1998-12-15 | Duke University | Culturing monocytes with IL-4, TNF-α and GM-CSF TO induce differentiation to dendric cells |
US5792105A (en) | 1996-09-11 | 1998-08-11 | Boston Scientific Corporation | Multichannel balloon catheter for delivering fluid |
US5868719A (en) | 1997-01-15 | 1999-02-09 | Boston Scientific Corporation | Drug delivery balloon catheter device |
US6406705B1 (en) | 1997-03-10 | 2002-06-18 | University Of Iowa Research Foundation | Use of nucleic acids containing unmethylated CpG dinucleotide as an adjuvant |
US5933145A (en) | 1997-04-17 | 1999-08-03 | Microsoft Corporation | Method and system for visually indicating a selection query |
US5866561A (en) | 1997-08-21 | 1999-02-02 | Scimed Life Systems, Inc. | Local delivery of estrogen for angiogenesis |
US6037323A (en) | 1997-09-29 | 2000-03-14 | Jean-Louis Dasseux | Apolipoprotein A-I agonists and their use to treat dyslipidemic disorders |
US6004925A (en) * | 1997-09-29 | 1999-12-21 | J. L. Dasseux | Apolipoprotein A-I agonists and their use to treat dyslipidemic disorders |
US6046166A (en) | 1997-09-29 | 2000-04-04 | Jean-Louis Dasseux | Apolipoprotein A-I agonists and their use to treat dyslipidemic disorders |
US5908413A (en) | 1997-10-03 | 1999-06-01 | Scimed Life Systems, Inc. | Radiopaque catheter and method of manufacture thereof |
AU2001247924A1 (en) | 2000-03-29 | 2001-10-08 | Aradigm Corporation | Cationic liposomes |
DE60117781T2 (de) | 2000-04-21 | 2006-11-23 | Amgen Inc., Thousand Oaks | Peptidderivate des apolipoproteins-a1/aii |
US7144862B2 (en) | 2000-08-24 | 2006-12-05 | The Regents Of The University Of California | Orally administered peptides to ameliorate atherosclerosis |
CA2435123A1 (en) | 2001-01-18 | 2002-07-25 | Newcastle University Ventures Ltd. | Biosensor with covalently attached membrane-spanning proteins |
US7803405B2 (en) | 2002-05-17 | 2010-09-28 | The Penn State Research Foundation | Encapsulation of aqueous phase systems within microscopic volumes |
WO2003099261A1 (en) | 2002-05-20 | 2003-12-04 | Oradel Medical Ltd. | Liposome drug delivery |
US7071163B2 (en) | 2002-08-05 | 2006-07-04 | Mirus Bio Corporation | Compounds for targeting hepatocytes in vivo |
US20040157253A1 (en) | 2003-02-07 | 2004-08-12 | Millennium Pharmaceuticals, Inc. | Methods and compositions for use of inflammatory proteins in the diagnosis and treatment of metabolic disorders |
AU2005220874B2 (en) | 2004-03-04 | 2010-12-23 | Vanderbilt University | Cell-penetrating SOCS polypeptides that inhibit cytokine-induced signaling |
US7108870B2 (en) | 2004-04-13 | 2006-09-19 | Council Of Scientific & Industrial Research | Process for isolation of withaferin-A from plant materials and products therefrom |
US7569546B2 (en) | 2004-07-16 | 2009-08-04 | Trustees Of Tufts College | Apolipoprotein A1 mimetics and uses thereof |
ES2625905T3 (es) | 2004-10-01 | 2017-07-20 | Midatech Ltd. | Nanopartículas que comprenden antígenos y adyuvantes capaces de estimular linfocitos T cooperadores |
US7220549B2 (en) | 2004-12-30 | 2007-05-22 | Helicos Biosciences Corporation | Stabilizing a nucleic acid for nucleic acid sequencing |
US7283337B2 (en) | 2005-03-04 | 2007-10-16 | Headway Technologies, Inc. | Abutted exchange bias design for sensor stabilization |
JP2009514860A (ja) | 2005-11-02 | 2009-04-09 | エアリス セラピューティクス,インコーポレイテッド | ポリカチオン−ポリアニオンの複合体、組成物およびその使用方法 |
JP2010530433A (ja) | 2007-06-20 | 2010-09-09 | メルク・シャープ・エンド・ドーム・コーポレイション | Apoa−1ペプチド模倣体 |
US9173890B2 (en) | 2007-09-20 | 2015-11-03 | Abbott Cardiovascular Systems Inc. | Sustained release of Apo A-I mimetic peptides and methods of treatment |
BRPI0817664A2 (pt) | 2007-10-12 | 2015-03-24 | Massachusetts Inst Technology | Nanopartículas, método para preparar nanopartículas e método para tratar terapeuticamente ou profilaticamente um indivíduo |
BRPI0907008A2 (pt) | 2008-01-31 | 2015-07-07 | Alnylam Pharmaceuticals Inc | Métodos otimizados para liberação de dsrna alvejando o gene pcsk9 |
US20110065644A1 (en) | 2008-03-09 | 2011-03-17 | Intradigm Corporation | Compositions comprising human pcsk9 and apolipoprotein b sirna and methods of use |
US8883729B2 (en) | 2008-05-22 | 2014-11-11 | Lawrence Livermore National Security, Llc | Nanolipoprotein particles and related compositions, methods and systems |
US20110159023A1 (en) * | 2008-08-25 | 2011-06-30 | Solomon Langermann | Pd-1 antagonists and methods for treating infectious disease |
WO2010037408A1 (en) * | 2008-09-30 | 2010-04-08 | Curevac Gmbh | Composition comprising a complexed (m)rna and a naked mrna for providing or enhancing an immunostimulatory response in a mammal and uses thereof |
WO2010078536A1 (en) | 2009-01-05 | 2010-07-08 | Rxi Pharmaceuticals Corporation | Inhibition of pcsk9 through rnai |
WO2010083728A1 (en) | 2009-01-23 | 2010-07-29 | Dapeng Zhou | Nanoparticle formulated glycolipid antigens for immunotherapy |
CA2982157A1 (en) | 2009-02-16 | 2010-08-19 | Cerenis Therapeutics Holding Sa | Apolipoprotein a-i mimics |
KR20120050429A (ko) * | 2009-06-15 | 2012-05-18 | 알닐람 파마슈티칼스 인코포레이티드 | Pcsk9 유전자를 표적으로 하는 지질 제형된 dsrna |
GB0913442D0 (en) | 2009-07-31 | 2009-09-16 | Univ Ramot | Cell-targeting nanoparticles comprising polynucleotide agents and uses thereof |
EP2525780B1 (en) | 2010-01-19 | 2022-09-07 | Northwestern University | Synthetic nanostructures including nucleic acids and/or other entities |
SG184127A1 (en) | 2010-03-19 | 2012-10-30 | Massachusetts Inst Technology | Lipid vesicle compositions and methods of use |
BR112012029066A2 (pt) | 2010-05-14 | 2020-09-01 | The General Hospital Corporation | composições e processos de identificação de neoantígenos específicos de tumor. |
WO2011159717A1 (en) | 2010-06-14 | 2011-12-22 | Baylor Research Institute | Inhibition of pro-inflammatory cytokine induced response |
GB201017889D0 (en) | 2010-10-22 | 2010-12-01 | Univ Dublin | A polymeric nanoparticle |
US8598339B2 (en) | 2011-02-01 | 2013-12-03 | University Of Kansas | Withanolide isolated from Physalis longifolia and analogs and methods of use thereof |
SI2767546T1 (sl) * | 2011-02-07 | 2019-03-29 | Cerenis Therapeutics Holding Sa | Lipoproteinski kompleksi in izdelava ter uporaba le-teh |
US20140213502A1 (en) | 2011-04-29 | 2014-07-31 | United States Department of Health and Human Services | Chemical modification of apolipoprotein mimetic peptides for the production of therapeutic agents |
JP2014519493A (ja) | 2011-05-12 | 2014-08-14 | イッサム・リサーチ・ディベロップメント・カンパニー・オブ・ザ・ヘブルー・ユニバーシティ・オブ・エルサレム・リミテッド | ポリマー共役脂質を含むリポソームおよび関連用途 |
US20150064255A1 (en) | 2012-02-22 | 2015-03-05 | Northwestern University | Nanostructures for treating cancers and other conditions |
WO2014025890A1 (en) | 2012-08-10 | 2014-02-13 | University Of North Texas Health Science Center | Drug delivery vehicle comprising conjugates between targeting polyamino acids and fatty acids |
KR102341899B1 (ko) | 2013-04-07 | 2021-12-21 | 더 브로드 인스티튜트, 인코퍼레이티드 | 개인맞춤화 신생물 백신을 위한 조성물 및 방법 |
US20160213051A1 (en) | 2013-09-04 | 2016-07-28 | Ceradis B.V. | Processed edible product comprising a polyelectrolyte complex and an antimicrobial compound |
WO2016011049A2 (en) | 2014-07-14 | 2016-01-21 | Schwendeman Anna | Compositions and methods for disease treatment using nanoparticle delivered compounds |
WO2016154542A2 (en) | 2015-03-25 | 2016-09-29 | The Regents Of The University Of Michigan | Compositions and methods for treating cardiovascular related disorders |
CA2979712C (en) * | 2015-03-25 | 2024-01-23 | The Regents Of The University Of Michigan | Nanoparticle compositions for delivery of biomacromolecules |
US20210106538A1 (en) | 2016-06-20 | 2021-04-15 | The Regents Of The University Of Michigan | Compositions and methods for delivery of biomacromolecule agents |
-
2016
- 2016-03-25 CA CA2979712A patent/CA2979712C/en active Active
- 2016-03-25 US US15/561,374 patent/US11219673B2/en active Active
- 2016-03-25 AU AU2016238290A patent/AU2016238290B9/en active Active
- 2016-03-25 MX MX2017012131A patent/MX2017012131A/es unknown
- 2016-03-25 WO PCT/US2016/024233 patent/WO2016154544A1/en active Application Filing
- 2016-03-25 BR BR112017020491-6A patent/BR112017020491A2/pt active Search and Examination
- 2016-03-25 EP EP16769774.7A patent/EP3273944A4/en active Pending
- 2016-03-25 JP JP2017550227A patent/JP2018516847A/ja active Pending
-
2017
- 2017-09-25 MX MX2023000745A patent/MX2023000745A/es unknown
-
2019
- 2019-09-05 AU AU2019226197A patent/AU2019226197B2/en active Active
-
2020
- 2020-01-10 JP JP2020002708A patent/JP6933403B2/ja active Active
-
2021
- 2021-08-12 JP JP2021131737A patent/JP7244124B2/ja active Active
- 2021-10-14 US US17/501,576 patent/US11833196B2/en active Active
-
2022
- 2022-08-25 AU AU2022221504A patent/AU2022221504A1/en active Pending
-
2023
- 2023-03-02 JP JP2023031818A patent/JP2023071864A/ja active Pending
- 2023-12-05 US US18/529,758 patent/US20240115679A1/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2002500165A (ja) | 1997-12-31 | 2002-01-08 | オラソマル テクノロジーズ,インコーポレーテッド | 新規の重合性の脂肪酸、リン脂質、及びそれから得られた重合リポソーム |
JP2011528371A (ja) | 2008-07-15 | 2011-11-17 | ノバルティス アーゲー | 免疫原性の両親媒性ペプチド組成物 |
JP2013540106A (ja) | 2010-08-30 | 2013-10-31 | エフ.ホフマン−ラ ロシュ アーゲー | テトラネクチン−アポリポタンパク質a−i、それを含有する脂質粒子及びその使用 |
WO2014096179A1 (en) | 2012-12-19 | 2014-06-26 | Novo Nordisk A/S | Novel glp-1 receptor agonists with cholesterol efflux activity |
Also Published As
Publication number | Publication date |
---|---|
BR112017020491A2 (pt) | 2018-07-17 |
US11833196B2 (en) | 2023-12-05 |
JP2020073568A (ja) | 2020-05-14 |
US11219673B2 (en) | 2022-01-11 |
JP6933403B2 (ja) | 2021-09-08 |
JP2021181484A (ja) | 2021-11-25 |
AU2019226197B2 (en) | 2022-05-26 |
US20220040276A1 (en) | 2022-02-10 |
EP3273944A4 (en) | 2019-02-27 |
EP3273944A1 (en) | 2018-01-31 |
WO2016154544A1 (en) | 2016-09-29 |
JP2023071864A (ja) | 2023-05-23 |
AU2019226197A1 (en) | 2019-09-26 |
CA2979712C (en) | 2024-01-23 |
US20180078625A1 (en) | 2018-03-22 |
US20240115679A1 (en) | 2024-04-11 |
MX2017012131A (es) | 2018-06-15 |
AU2016238290B2 (en) | 2019-06-06 |
JP2018516847A (ja) | 2018-06-28 |
AU2016238290B9 (en) | 2019-06-13 |
CA2979712A1 (en) | 2016-09-29 |
AU2022221504A1 (en) | 2022-09-22 |
AU2016238290A1 (en) | 2017-10-05 |
MX2023000745A (es) | 2023-02-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7244124B2 (ja) | 生体高分子薬を送達するための組成物及び方法 | |
JP2024028876A (ja) | 免疫応答を調節可能な金属含有製剤のための組成物および方法 | |
US20210106538A1 (en) | Compositions and methods for delivery of biomacromolecule agents | |
JP2023545466A (ja) | 免疫応答を調節することができる、金属イオンと会合したstingアゴニストの結晶多形体 | |
US20230310504A1 (en) | Platelet membrane coated nanoparticles and uses thereof | |
KR20240082378A (ko) | 면역 반응을 조절할 수 있는 금속 함유 제형의 조성물 및 방법 | |
Krishnamachari | PLGA microparticle based vaccine carriers for an improved and efficacious tumor therapy |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210910 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210910 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220920 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20230131 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20230302 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7244124 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |