JP2011529912A

JP2011529912A - 核酸送達システム用のナノ粒子組成物

核酸送達システム用のナノ粒子組成物 Download PDF

Info

Publication number: JP2011529912A
Authority: JP; Japan
Prior art keywords: nanoparticles; peg; nanoparticle; oligonucleotide; nanoparticle composition
Prior art date: 2008-07-31
Legal status : Pending

Application number

JP2011521353A

Other languages

English (en)

Japanese (ja)

Other versions

JP2011529912A5 (https=

Inventor

ヅァオ，ホン

シー，リャンジュン

Original Assignee

エンゾンファーマシューティカルズ，インコーポレーテッド

Priority date

2008-07-31

Filing date

2009-07-31

Publication date

2011-12-15

2009-07-31 Application filed by エンゾンファーマシューティカルズ，インコーポレーテッド filed Critical エンゾンファーマシューティカルズ，インコーポレーテッド

2011-12-15 Publication of JP2011529912A publication Critical patent/JP2011529912A/ja

2012-07-26 Publication of JP2011529912A5 publication Critical patent/JP2011529912A5/ja

Status Pending legal-status Critical Current

Links

239000002105 nanoparticle Substances 0.000 title claims abstract description 376
239000000203 mixture Substances 0.000 title claims abstract description 154
150000007523 nucleic acids Chemical class 0.000 title claims description 111
102000039446 nucleic acids Human genes 0.000 title claims description 106
108020004707 nucleic acids Proteins 0.000 title claims description 106
238000012384 transportation and delivery Methods 0.000 title abstract description 25
108091034117 Oligonucleotide Proteins 0.000 claims abstract description 158
150000002632 lipids Chemical class 0.000 claims abstract description 108
238000000034 method Methods 0.000 claims abstract description 82
108090000623 proteins and genes Proteins 0.000 claims abstract description 71
230000014509 gene expression Effects 0.000 claims abstract description 68
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 abstract description 64
125000002091 cationic group Chemical group 0.000 claims abstract description 46
230000000799 fusogenic effect Effects 0.000 claims abstract description 28
210000004027 cell Anatomy 0.000 claims description 118
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound 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 claims description 100
-1 cationic lipid Chemical class 0.000 claims description 95
206010028980 Neoplasm Diseases 0.000 claims description 78
201000011510 cancer Diseases 0.000 claims description 57
235000012000 cholesterol Nutrition 0.000 claims description 47
230000000692 anti-sense effect Effects 0.000 claims description 44
125000000217 alkyl group Chemical group 0.000 claims description 40
239000002773 nucleotide Substances 0.000 claims description 29
229910052739 hydrogen Inorganic materials 0.000 claims description 25
239000001257 hydrogen Substances 0.000 claims description 23
125000003729 nucleotide group Chemical group 0.000 claims description 22
239000000074 antisense oligonucleotide Substances 0.000 claims description 20
238000012230 antisense oligonucleotides Methods 0.000 claims description 20
229940106189 ceramide Drugs 0.000 claims description 20
241000124008 Mammalia Species 0.000 claims description 19
229910052760 oxygen Inorganic materials 0.000 claims description 18
150000008104 phosphatidylethanolamines Chemical class 0.000 claims description 18
JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 16
210000004185 liver Anatomy 0.000 claims description 15
229910052717 sulfur Inorganic materials 0.000 claims description 15
YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 claims description 13
ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 claims description 13
VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 claims description 13
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 claims description 12
CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
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 claims description 10
108020004459 Small interfering RNA Proteins 0.000 claims description 9
108010002687 Survivin Proteins 0.000 claims description 9
239000004055 small Interfering RNA Substances 0.000 claims description 9
RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 9
102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 claims description 8
102100021663 Baculoviral IAP repeat-containing protein 5 Human genes 0.000 claims description 8
239000002246 antineoplastic agent Substances 0.000 claims description 8
229940127089 cytotoxic agent Drugs 0.000 claims description 7
230000002401 inhibitory effect Effects 0.000 claims description 7
101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
108700011259 MicroRNAs Proteins 0.000 claims description 5
108700020796 Oncogene Proteins 0.000 claims description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
230000002222 downregulating effect Effects 0.000 claims description 5
230000004663 cell proliferation Effects 0.000 claims description 4
108091023037 Aptamer Proteins 0.000 claims description 3
102000053642 Catalytic RNA Human genes 0.000 claims description 3
108090000994 Catalytic RNA Proteins 0.000 claims description 3
230000010261 cell growth Effects 0.000 claims description 3
210000005260 human cell Anatomy 0.000 claims description 3
239000012678 infectious agent Substances 0.000 claims description 3
206010061289 metastatic neoplasm Diseases 0.000 claims description 3
239000002679 microRNA Substances 0.000 claims description 3
230000037361 pathway Effects 0.000 claims description 3
230000004647 pro-inflammatory pathway Effects 0.000 claims description 3
108091092562 ribozyme Proteins 0.000 claims description 3
230000003612 virological effect Effects 0.000 claims description 3
108091030071 RNAI Proteins 0.000 claims description 2
230000009368 gene silencing by RNA Effects 0.000 claims description 2
230000001394 metastastic effect Effects 0.000 claims description 2
230000006482 proangiogenic pathway Effects 0.000 claims description 2
108091093037 Peptide nucleic acid Proteins 0.000 claims 2
108700026220 vif Genes Proteins 0.000 claims 2
108060000903 Beta-catenin Proteins 0.000 claims 1
102000015735 Beta-catenin Human genes 0.000 claims 1
108091028664 Ribonucleotide Proteins 0.000 claims 1
239000002336 ribonucleotide Substances 0.000 claims 1
125000002652 ribonucleotide group Chemical group 0.000 claims 1
229920001223 polyethylene glycol Chemical class 0.000 description 70
239000002202 Polyethylene glycol Chemical class 0.000 description 68
230000000694 effects Effects 0.000 description 51
108020004999 messenger RNA Proteins 0.000 description 36
238000011282 treatment Methods 0.000 description 36
238000000338 in vitro Methods 0.000 description 35
230000003828 downregulation Effects 0.000 description 27
238000001727 in vivo Methods 0.000 description 27
230000001225 therapeutic effect Effects 0.000 description 25
239000000243 solution Substances 0.000 description 24
150000001875 compounds Chemical class 0.000 description 22
102000004169 proteins and genes Human genes 0.000 description 21
108090000765 processed proteins & peptides Proteins 0.000 description 19
210000001519 tissue Anatomy 0.000 description 19
238000002360 preparation method Methods 0.000 description 18
241000699670 Mus sp. Species 0.000 description 17
125000003118 aryl group Chemical group 0.000 description 17
MWRBNPKJOOWZPW-CLFAGFIQSA-N dioleoyl phosphatidylethanolamine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C/CCCCCCCC MWRBNPKJOOWZPW-CLFAGFIQSA-N 0.000 description 17
206010060862 Prostate cancer Diseases 0.000 description 16
208000000236 Prostatic Neoplasms Diseases 0.000 description 16
230000005764 inhibitory process Effects 0.000 description 16
150000001412 amines Chemical class 0.000 description 15
108020000948 Antisense Oligonucleotides Proteins 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 13
238000009472 formulation Methods 0.000 description 13
150000003839 salts Chemical class 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
239000003795 chemical substances by application Substances 0.000 description 12
125000000592 heterocycloalkyl group Chemical group 0.000 description 12
229920000642 polymer Polymers 0.000 description 12
239000000725 suspension Substances 0.000 description 12
210000004881 tumor cell Anatomy 0.000 description 12
201000010099 disease Diseases 0.000 description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
125000001072 heteroaryl group Chemical group 0.000 description 11
230000003834 intracellular effect Effects 0.000 description 11
230000004048 modification Effects 0.000 description 11
238000012986 modification Methods 0.000 description 11
239000008194 pharmaceutical composition Substances 0.000 description 11
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
125000003545 alkoxy group Chemical group 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
125000000304 alkynyl group Chemical group 0.000 description 9
239000007864 aqueous solution Substances 0.000 description 9
230000008901 benefit Effects 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol Substances OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
229910052757 nitrogen Inorganic materials 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
230000008685 targeting Effects 0.000 description 9
238000001890 transfection Methods 0.000 description 9
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 description 8
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 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
206010009944 Colon cancer Diseases 0.000 description 8
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
125000002252 acyl group Chemical group 0.000 description 8
125000003342 alkenyl group Chemical group 0.000 description 8
239000000872 buffer Substances 0.000 description 8
230000000295 complement effect Effects 0.000 description 8
229940125898 compound 5 Drugs 0.000 description 8
125000004093 cyano group Chemical group *C#N 0.000 description 8
125000000753 cycloalkyl group Chemical group 0.000 description 8
238000002296 dynamic light scattering Methods 0.000 description 8
125000005647 linker group Chemical group 0.000 description 8
230000007935 neutral effect Effects 0.000 description 8
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
235000018102 proteins Nutrition 0.000 description 8
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 7
206010058467 Lung neoplasm malignant Diseases 0.000 description 7
206010027476 Metastases Diseases 0.000 description 7
108091028043 Nucleic acid sequence Proteins 0.000 description 7
208000005718 Stomach Neoplasms Diseases 0.000 description 7
150000001841 cholesterols Chemical class 0.000 description 7
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 7
206010017758 gastric cancer Diseases 0.000 description 7
201000005202 lung cancer Diseases 0.000 description 7
208000020816 lung neoplasm Diseases 0.000 description 7
239000000463 material Substances 0.000 description 7
230000009401 metastasis Effects 0.000 description 7
239000000902 placebo Substances 0.000 description 7
229940068196 placebo Drugs 0.000 description 7
102000004196 processed proteins & peptides Human genes 0.000 description 7
201000011549 stomach cancer Diseases 0.000 description 7
238000002560 therapeutic procedure Methods 0.000 description 7
LVNGJLRDBYCPGB-UHFFFAOYSA-N 1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-UHFFFAOYSA-N 0.000 description 6
206010006187 Breast cancer Diseases 0.000 description 6
208000026310 Breast neoplasm Diseases 0.000 description 6
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
239000004698 Polyethylene Substances 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
125000004183 alkoxy alkyl group Chemical group 0.000 description 6
125000006350 alkyl thio alkyl group Chemical group 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
OTBHHUPVCYLGQO-UHFFFAOYSA-N bis(3-aminopropyl)amine Chemical compound NCCCNCCCN OTBHHUPVCYLGQO-UHFFFAOYSA-N 0.000 description 6
229940125782 compound 2 Drugs 0.000 description 6
231100000673 dose–response relationship Toxicity 0.000 description 6
239000003814 drug Substances 0.000 description 6
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 6
125000005843 halogen group Chemical group 0.000 description 6
238000002347 injection Methods 0.000 description 6
239000007924 injection Substances 0.000 description 6
239000002502 liposome Substances 0.000 description 6
230000002829 reductive effect Effects 0.000 description 6
239000011780 sodium chloride Substances 0.000 description 6
239000007787 solid Substances 0.000 description 6
108091032973 (ribonucleotides)n+m Proteins 0.000 description 5
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 5
229960000549 4-dimethylaminophenol Drugs 0.000 description 5
IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical class NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 5
108020004414 DNA Proteins 0.000 description 5
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical group NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 5
RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 5
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 5
125000003282 alkyl amino group Chemical group 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
208000029742 colonic neoplasm Diseases 0.000 description 5
229940126214 compound 3 Drugs 0.000 description 5
OGQYPPBGSLZBEG-UHFFFAOYSA-N dimethyl(dioctadecyl)azanium Chemical compound CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC OGQYPPBGSLZBEG-UHFFFAOYSA-N 0.000 description 5
229940079593 drug Drugs 0.000 description 5
238000005516 engineering process Methods 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
239000002609 medium Substances 0.000 description 5
125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
239000002245 particle Substances 0.000 description 5
150000003904 phospholipids Chemical class 0.000 description 5
239000000126 substance Substances 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
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 4
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 4
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
IHNKQIMGVNPMTC-RUZDIDTESA-N 1-stearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C IHNKQIMGVNPMTC-RUZDIDTESA-N 0.000 description 4
108091003079 Bovine Serum Albumin Proteins 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 4
102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 4
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
239000012124 Opti-MEM Substances 0.000 description 4
229910019142 PO4 Inorganic materials 0.000 description 4
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 4
NONFBHXKNNVFMO-UHFFFAOYSA-N [2-aminoethoxy(tetradecanoyloxy)phosphoryl] tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OP(=O)(OCCN)OC(=O)CCCCCCCCCCCCC NONFBHXKNNVFMO-UHFFFAOYSA-N 0.000 description 4
AMTCKRZHSPPHSE-UHFFFAOYSA-N [N-]=[N+]=NON=[N+]=[N-] Chemical compound [N-]=[N+]=NON=[N+]=[N-] AMTCKRZHSPPHSE-UHFFFAOYSA-N 0.000 description 4
239000002253 acid Substances 0.000 description 4
239000000654 additive Substances 0.000 description 4
125000005103 alkyl silyl group Chemical group 0.000 description 4
125000004414 alkyl thio group Chemical group 0.000 description 4
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 4
239000000427 antigen Substances 0.000 description 4
108091007433 antigens Proteins 0.000 description 4
102000036639 antigens Human genes 0.000 description 4
125000002029 aromatic hydrocarbon group Chemical group 0.000 description 4
150000001720 carbohydrates Chemical class 0.000 description 4
239000007822 coupling agent Substances 0.000 description 4
OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
150000001982 diacylglycerols Chemical class 0.000 description 4
238000000502 dialysis Methods 0.000 description 4
238000010790 dilution Methods 0.000 description 4
239000012895 dilution Substances 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
239000012091 fetal bovine serum Substances 0.000 description 4
239000011724 folic acid Substances 0.000 description 4
235000019152 folic acid Nutrition 0.000 description 4
102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 4
108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
239000002777 nucleoside Substances 0.000 description 4
235000021317 phosphate Nutrition 0.000 description 4
108091033319 polynucleotide Proteins 0.000 description 4
102000040430 polynucleotide Human genes 0.000 description 4
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
239000001267 polyvinylpyrrolidone Substances 0.000 description 4
229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
239000000047 product Substances 0.000 description 4
UCQFSGCWHRTMGG-UHFFFAOYSA-N pyrazole-1-carboximidamide Chemical compound NC(=N)N1C=CC=N1 UCQFSGCWHRTMGG-UHFFFAOYSA-N 0.000 description 4
IUCJMVBFZDHPDX-UHFFFAOYSA-N tretamine Chemical compound C1CN1C1=NC(N2CC2)=NC(N2CC2)=N1 IUCJMVBFZDHPDX-UHFFFAOYSA-N 0.000 description 4
125000004953 trihalomethyl group Chemical group 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
230000003442 weekly effect Effects 0.000 description 4
FVXDQWZBHIXIEJ-LNDKUQBDSA-N 1,2-di-[(9Z,12Z)-octadecadienoyl]-sn-glycero-3-phosphocholine Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC FVXDQWZBHIXIEJ-LNDKUQBDSA-N 0.000 description 3
OQQOAWVKVDAJOI-VWLOTQADSA-N 1,2-dilauroyl-sn-glycerol Chemical compound CCCCCCCCCCCC(=O)OC[C@H](CO)OC(=O)CCCCCCCCCCC OQQOAWVKVDAJOI-VWLOTQADSA-N 0.000 description 3
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 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
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 3
ASWBNKHCZGQVJV-HSZRJFAPSA-N 1-hexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-HSZRJFAPSA-N 0.000 description 3
NNWAARLSYSBVPB-UHFFFAOYSA-N 1h-imidazole-4,5-dicarboxamide Chemical compound NC(=O)C=1N=CNC=1C(N)=O NNWAARLSYSBVPB-UHFFFAOYSA-N 0.000 description 3
PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 3
208000003174 Brain Neoplasms Diseases 0.000 description 3
108010051109 Cell-Penetrating Peptides Proteins 0.000 description 3
102000020313 Cell-Penetrating Peptides Human genes 0.000 description 3
206010008342 Cervix carcinoma Diseases 0.000 description 3
208000001333 Colorectal Neoplasms Diseases 0.000 description 3
102000009024 Epidermal Growth Factor Human genes 0.000 description 3
ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 3
206010025323 Lymphomas Diseases 0.000 description 3
241000699666 Mus <mouse, genus> Species 0.000 description 3
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 3
206010033128 Ovarian cancer Diseases 0.000 description 3
206010061535 Ovarian neoplasm Diseases 0.000 description 3
206010061902 Pancreatic neoplasm Diseases 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
108091081021 Sense strand Proteins 0.000 description 3
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 3
FPKBIYKAYFGTKG-UHFFFAOYSA-N [5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[2-[[[5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[5-(2-amino-6-oxo-1H-purin-9-yl)-2-[[[2-[[[2-[[[5-(2-amino-6-oxo-1H-purin-9-yl)-2-(hydroxymethyl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(6-aminopurin-9-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-3-yl]oxy-hydroxyphosphoryl]oxymethyl]oxolan-3-yl] [3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-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]methyl hydrogen phosphate Chemical compound Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3O)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(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O FPKBIYKAYFGTKG-UHFFFAOYSA-N 0.000 description 3
IBXPAFBDJCXCDW-MHFPCNPESA-A [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].Cc1cn([C@H]2C[C@H](O)[C@@H](COP([S-])(=O)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3CO)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c3nc(N)[nH]c4=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].Cc1cn([C@H]2C[C@H](O)[C@@H](COP([S-])(=O)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3COP([O-])(=S)O[C@H]3C[C@@H](O[C@@H]3CO)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c3nc(N)[nH]c4=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3cnc4c3nc(N)[nH]c4=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O IBXPAFBDJCXCDW-MHFPCNPESA-A 0.000 description 3
239000013543 active substance Substances 0.000 description 3
125000004423 acyloxy group Chemical group 0.000 description 3
125000000129 anionic group Chemical group 0.000 description 3
108010072041 arginyl-glycyl-aspartic acid Proteins 0.000 description 3
230000005907 cancer growth Effects 0.000 description 3
235000014633 carbohydrates Nutrition 0.000 description 3
239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
230000001413 cellular effect Effects 0.000 description 3
201000010881 cervical cancer Diseases 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
229940125904 compound 1 Drugs 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
235000014113 dietary fatty acids Nutrition 0.000 description 3
NAGJZTKCGNOGPW-UHFFFAOYSA-K dioxido-sulfanylidene-sulfido-$l^{5}-phosphane Chemical compound [O-]P([O-])([S-])=S NAGJZTKCGNOGPW-UHFFFAOYSA-K 0.000 description 3
ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 description 3
238000005538 encapsulation Methods 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
239000000194 fatty acid Substances 0.000 description 3
229930195729 fatty acid Natural products 0.000 description 3
150000004665 fatty acids Chemical class 0.000 description 3
238000001914 filtration Methods 0.000 description 3
229960000304 folic acid Drugs 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
238000010255 intramuscular injection Methods 0.000 description 3
239000007927 intramuscular injection Substances 0.000 description 3
208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000011259 mixed solution Substances 0.000 description 3
238000002156 mixing Methods 0.000 description 3
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
125000003835 nucleoside group Chemical group 0.000 description 3
229960000435 oblimersen Drugs 0.000 description 3
125000002811 oleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
201000002528 pancreatic cancer Diseases 0.000 description 3
208000008443 pancreatic carcinoma Diseases 0.000 description 3
150000003905 phosphatidylinositols Chemical class 0.000 description 3
239000013612 plasmid Substances 0.000 description 3
229920000573 polyethylene Polymers 0.000 description 3
239000002157 polynucleotide Substances 0.000 description 3
238000000746 purification Methods 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
230000002441 reversible effect Effects 0.000 description 3
239000002904 solvent Substances 0.000 description 3
125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
125000001424 substituent group Chemical group 0.000 description 3
125000000547 substituted alkyl group Chemical group 0.000 description 3
235000000346 sugar Nutrition 0.000 description 3
239000011593 sulfur Chemical group 0.000 description 3
230000002195 synergetic effect Effects 0.000 description 3
QQWYQAQQADNEIC-RVDMUPIBSA-N tert-butyl [(z)-[cyano(phenyl)methylidene]amino] carbonate Chemical compound CC(C)(C)OC(=O)O\N=C(/C#N)C1=CC=CC=C1 QQWYQAQQADNEIC-RVDMUPIBSA-N 0.000 description 3
238000012360 testing method Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
238000012447 xenograft mouse model Methods 0.000 description 3
NEZDNQCXEZDCBI-WJOKGBTCSA-N (2-aminoethoxy)[(2r)-2,3-bis(tetradecanoyloxy)propoxy]phosphinic acid Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCC NEZDNQCXEZDCBI-WJOKGBTCSA-N 0.000 description 2
JSPNNZKWADNWHI-PNANGNLXSA-N (2r)-2-hydroxy-n-[(2s,3r,4e,8e)-3-hydroxy-9-methyl-1-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoctadeca-4,8-dien-2-yl]heptadecanamide Chemical compound CCCCCCCCCCCCCCC[C@@H](O)C(=O)N[C@H]([C@H](O)\C=C\CC\C=C(/C)CCCCCCCCC)CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O JSPNNZKWADNWHI-PNANGNLXSA-N 0.000 description 2
XUNKPNYCNUKOAU-VXJRNSOOSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]a Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O XUNKPNYCNUKOAU-VXJRNSOOSA-N 0.000 description 2
SJHPCNCNNSSLPL-CSKARUKUSA-N (4e)-4-(ethoxymethylidene)-2-phenyl-1,3-oxazol-5-one Chemical compound O1C(=O)C(=C/OCC)\N=C1C1=CC=CC=C1 SJHPCNCNNSSLPL-CSKARUKUSA-N 0.000 description 2
125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 description 2
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 2
LVNGJLRDBYCPGB-LDLOPFEMSA-N (R)-1,2-distearoylphosphatidylethanolamine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCCCCCCCCCCCC LVNGJLRDBYCPGB-LDLOPFEMSA-N 0.000 description 2
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 description 2
MLKLDGSYMHFAOC-AREMUKBSSA-N 1,2-dicapryl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCC MLKLDGSYMHFAOC-AREMUKBSSA-N 0.000 description 2
BIABMEZBCHDPBV-BEBVUIBBSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoglycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCCCC BIABMEZBCHDPBV-BEBVUIBBSA-N 0.000 description 2
KLFKZIQAIPDJCW-GPOMZPHUSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCC KLFKZIQAIPDJCW-GPOMZPHUSA-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
IJFVSSZAOYLHEE-SSEXGKCCSA-N 1,2-dilauroyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCC IJFVSSZAOYLHEE-SSEXGKCCSA-N 0.000 description 2
UHUSDOQQWJGJQS-QNGWXLTQSA-N 1,2-dioctadecanoyl-sn-glycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](CO)OC(=O)CCCCCCCCCCCCCCCCC UHUSDOQQWJGJQS-QNGWXLTQSA-N 0.000 description 2
WTBFLCSPLLEDEM-JIDRGYQWSA-N 1,2-dioleoyl-sn-glycero-3-phospho-L-serine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC WTBFLCSPLLEDEM-JIDRGYQWSA-N 0.000 description 2
JEJLGIQLPYYGEE-XIFFEERXSA-N 1,2-dipalmitoyl-sn-glycerol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](CO)OC(=O)CCCCCCCCCCCCCCC JEJLGIQLPYYGEE-XIFFEERXSA-N 0.000 description 2
UKDDQGWMHWQMBI-UHFFFAOYSA-O 1,2-diphytanoyl-sn-glycero-3-phosphocholine Chemical compound CC(C)CCCC(C)CCCC(C)CCCC(C)CC(=O)OCC(COP(O)(=O)OCC[N+](C)(C)C)OC(=O)CC(C)CCCC(C)CCCC(C)CCCC(C)C UKDDQGWMHWQMBI-UHFFFAOYSA-O 0.000 description 2
JFBCSFJKETUREV-LJAQVGFWSA-N 1,2-ditetradecanoyl-sn-glycerol Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](CO)OC(=O)CCCCCCCCCCCCC JFBCSFJKETUREV-LJAQVGFWSA-N 0.000 description 2
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 2
MPCAJMNYNOGXPB-UHFFFAOYSA-N 1,5-anhydrohexitol Chemical class OCC1OCC(O)C(O)C1O MPCAJMNYNOGXPB-UHFFFAOYSA-N 0.000 description 2
RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 description 2
JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 2
PAZGBAOHGQRCBP-HGWHEPCSSA-N 1-hexadecanoyl-2-[(9Z)-octadec-9-enoyl]-sn-glycero-3-phospho-(1'-sn-glycerol) Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCC\C=C/CCCCCCCC PAZGBAOHGQRCBP-HGWHEPCSSA-N 0.000 description 2
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 2
TYAQXZHDAGZOEO-KXQOOQHDSA-N 1-myristoyl-2-stearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCC TYAQXZHDAGZOEO-KXQOOQHDSA-N 0.000 description 2
VXUOFDJKYGDUJI-OAQYLSRUSA-N 1-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C VXUOFDJKYGDUJI-OAQYLSRUSA-N 0.000 description 2
MZWGYEJOZNRLQE-KXQOOQHDSA-N 1-stearoyl-2-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCC MZWGYEJOZNRLQE-KXQOOQHDSA-N 0.000 description 2
LDGWQMRUWMSZIU-LQDDAWAPSA-M 2,3-bis[(z)-octadec-9-enoxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)C)OCCCCCCCC\C=C/CCCCCCCC LDGWQMRUWMSZIU-LQDDAWAPSA-M 0.000 description 2
KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 2
ZLGYVWRJIZPQMM-HHHXNRCGSA-N 2-azaniumylethyl [(2r)-2,3-di(dodecanoyloxy)propyl] phosphate Chemical compound CCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCC ZLGYVWRJIZPQMM-HHHXNRCGSA-N 0.000 description 2
JQKOHRZNEOQNJE-ZZEZOPTASA-N 2-azaniumylethyl [3-octadecanoyloxy-2-[(z)-octadec-9-enoyl]oxypropyl] phosphate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COP([O-])(=O)OCC[NH3+])OC(=O)CCCCCCC\C=C/CCCCCCCC JQKOHRZNEOQNJE-ZZEZOPTASA-N 0.000 description 2
FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 2
LZINOQJQXIEBNN-UHFFFAOYSA-N 4-hydroxybutyl dihydrogen phosphate Chemical compound OCCCCOP(O)(O)=O LZINOQJQXIEBNN-UHFFFAOYSA-N 0.000 description 2
YSFGBPCBPNVLOK-UHFFFAOYSA-N 6-hydroxy-2-methylhex-2-enamide Chemical compound NC(=O)C(C)=CCCCO YSFGBPCBPNVLOK-UHFFFAOYSA-N 0.000 description 2
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 2
108700026758 Adenovirus hexon capsid Proteins 0.000 description 2
102100026882 Alpha-synuclein Human genes 0.000 description 2
101710085003 Alpha-tubulin N-acetyltransferase Proteins 0.000 description 2
101710085461 Alpha-tubulin N-acetyltransferase 1 Proteins 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
108010025628 Apolipoproteins E Proteins 0.000 description 2
102000013918 Apolipoproteins E Human genes 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
QPYUGOUSOOCGGQ-UHFFFAOYSA-N CN(CCCN(CCCCN(CCC(N(CCCCCCCCCCCC)CCCCCCCCCCCC)(CCCCCCCCCCCC)CCCCCCCCCCCC)C)C)C Chemical compound CN(CCCN(CCCCN(CCC(N(CCCCCCCCCCCC)CCCCCCCCCCCC)(CCCCCCCCCCCC)CCCCCCCCCCCC)C)C)C QPYUGOUSOOCGGQ-UHFFFAOYSA-N 0.000 description 2
QBJFCIRZABYLPK-UHFFFAOYSA-N CN(CCCN(CCCCN(CCC(N(CCCCCCCCCCCCCC)CCCCCCCCCCCCCC)(CCCCCCCCCCCCCC)CCCCCCCCCCCCCC)C)C)C Chemical compound CN(CCCN(CCCCN(CCC(N(CCCCCCCCCCCCCC)CCCCCCCCCCCCCC)(CCCCCCCCCCCCCC)CCCCCCCCCCCCCC)C)C)C QBJFCIRZABYLPK-UHFFFAOYSA-N 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
102000053602 DNA Human genes 0.000 description 2
XULFJDKZVHTRLG-JDVCJPALSA-N DOSPA trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F.CCCCCCCC\C=C/CCCCCCCCOCC(C[N+](C)(C)CCNC(=O)C(CCCNCCCN)NCCCN)OCCCCCCCC\C=C/CCCCCCCC XULFJDKZVHTRLG-JDVCJPALSA-N 0.000 description 2
229920002307 Dextran Polymers 0.000 description 2
GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
102000001301 EGF receptor Human genes 0.000 description 2
108060006698 EGF receptor Proteins 0.000 description 2
102000056372 ErbB-3 Receptor Human genes 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
244000068988 Glycine max Species 0.000 description 2
235000010469 Glycine max Nutrition 0.000 description 2
102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 2
101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 2
101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 description 2
108050009527 Hypoxia-inducible factor-1 alpha Proteins 0.000 description 2
206010061218 Inflammation Diseases 0.000 description 2
229910013684 LiClO 4 Inorganic materials 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
101710163270 Nuclease Proteins 0.000 description 2
102000043276 Oncogene Human genes 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
108010003541 Platelet Activating Factor Proteins 0.000 description 2
RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
108010001267 Protein Subunits Proteins 0.000 description 2
102000002067 Protein Subunits Human genes 0.000 description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
101001000212 Rattus norvegicus Decorin Proteins 0.000 description 2
101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 2
102000003800 Selectins Human genes 0.000 description 2
108090000184 Selectins Proteins 0.000 description 2
206010041067 Small cell lung cancer Diseases 0.000 description 2
229930182558 Sterol Natural products 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
239000007983 Tris buffer Substances 0.000 description 2
102100021869 Tyrosine aminotransferase Human genes 0.000 description 2
101710175714 Tyrosine aminotransferase Proteins 0.000 description 2
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
108700005077 Viral Genes Proteins 0.000 description 2
LHCZDUCPSRJDJT-PLYLYKGUSA-N [(2r)-3-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-2-dodecanoyloxypropyl] dodecanoate Chemical compound CCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCC LHCZDUCPSRJDJT-PLYLYKGUSA-N 0.000 description 2
FVJZSBGHRPJMMA-DHPKCYQYSA-N [(2r)-3-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-2-octadecanoyloxypropyl] octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCCCCCC FVJZSBGHRPJMMA-DHPKCYQYSA-N 0.000 description 2
BPHQZTVXXXJVHI-IADGFXSZSA-N [(2r)-3-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-2-tetradecanoyloxypropyl] tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-IADGFXSZSA-N 0.000 description 2
QNEPTKZEXBPDLF-JDTILAPWSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] carbonochloridate Chemical compound C1C=C2C[C@@H](OC(Cl)=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 QNEPTKZEXBPDLF-JDTILAPWSA-N 0.000 description 2
SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 2
230000035508 accumulation Effects 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
230000004913 activation Effects 0.000 description 2
UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
238000010171 animal model Methods 0.000 description 2
230000000890 antigenic effect Effects 0.000 description 2
238000013459 approach Methods 0.000 description 2
125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000003710 aryl alkyl group Chemical group 0.000 description 2
125000005129 aryl carbonyl group Chemical group 0.000 description 2
125000005199 aryl carbonyloxy group Chemical group 0.000 description 2
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
238000003556 assay Methods 0.000 description 2
210000001124 body fluid Anatomy 0.000 description 2
239000010839 body fluid Substances 0.000 description 2
125000002837 carbocyclic group Chemical group 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
230000004700 cellular uptake Effects 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
229930183167 cerebroside Natural products 0.000 description 2
RIZIAUKTHDLMQX-UHFFFAOYSA-N cerebroside D Natural products CCCCCCCCCCCCCCCCC(O)C(=O)NC(C(O)C=CCCC=C(C)CCCCCCCCC)COC1OC(CO)C(O)C(O)C1O RIZIAUKTHDLMQX-UHFFFAOYSA-N 0.000 description 2
230000008859 change Effects 0.000 description 2
230000002596 correlated effect Effects 0.000 description 2
125000000392 cycloalkenyl group Chemical group 0.000 description 2
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
235000018417 cysteine Nutrition 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
150000001985 dialkylglycerols Chemical class 0.000 description 2
TXFOLHZMICYNRM-UHFFFAOYSA-N dichlorophosphoryloxybenzene Chemical compound ClP(Cl)(=O)OC1=CC=CC=C1 TXFOLHZMICYNRM-UHFFFAOYSA-N 0.000 description 2
BPHQZTVXXXJVHI-UHFFFAOYSA-N dimyristoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-UHFFFAOYSA-N 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
NFRFUGBXJTXTMZ-QYKZUBHNSA-L disodium;[(2r)-2,3-di(hexadecanoyloxy)propyl] phosphate Chemical compound [Na+].[Na+].CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])([O-])=O)OC(=O)CCCCCCCCCCCCCCC NFRFUGBXJTXTMZ-QYKZUBHNSA-L 0.000 description 2
238000004090 dissolution Methods 0.000 description 2
FVJZSBGHRPJMMA-UHFFFAOYSA-N distearoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCCCCCC FVJZSBGHRPJMMA-UHFFFAOYSA-N 0.000 description 2
238000009826 distribution Methods 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
230000009977 dual effect Effects 0.000 description 2
230000009881 electrostatic interaction Effects 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
210000002615 epidermis Anatomy 0.000 description 2
230000006870 function Effects 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
208000005017 glioblastoma Diseases 0.000 description 2
125000004404 heteroalkyl group Chemical group 0.000 description 2
JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
230000002209 hydrophobic effect Effects 0.000 description 2
230000001965 increasing effect Effects 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
230000004054 inflammatory process Effects 0.000 description 2
NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
238000007912 intraperitoneal administration Methods 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 2
125000000400 lauroyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000003446 ligand Substances 0.000 description 2
238000011068 loading method Methods 0.000 description 2
210000004962 mammalian cell Anatomy 0.000 description 2
PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 2
208000037819 metastatic cancer Diseases 0.000 description 2
208000011575 metastatic malignant neoplasm Diseases 0.000 description 2
125000001419 myristoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000012038 nucleophile Substances 0.000 description 2
229940046166 oligodeoxynucleotide Drugs 0.000 description 2
125000000962 organic group Chemical group 0.000 description 2
238000012856 packing Methods 0.000 description 2
SSZBUIDZHHWXNJ-UHFFFAOYSA-N palmityl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
MCYTYTUNNNZWOK-LCLOTLQISA-N penetratin Chemical compound C([C@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N)CCCNC(N)=N)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CC=CC=C1 MCYTYTUNNNZWOK-LCLOTLQISA-N 0.000 description 2
108010043655 penetratin Proteins 0.000 description 2
IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 2
150000008105 phosphatidylcholines Chemical class 0.000 description 2
229940067605 phosphatidylethanolamines Drugs 0.000 description 2
150000003014 phosphoric acid esters Chemical class 0.000 description 2
229920013639 polyalphaolefin Polymers 0.000 description 2
239000000843 powder Substances 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
239000001294 propane Substances 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical group CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
238000010839 reverse transcription Methods 0.000 description 2
150000004671 saturated fatty acids Chemical class 0.000 description 2
235000003441 saturated fatty acids Nutrition 0.000 description 2
150000003335 secondary amines Chemical class 0.000 description 2
210000002966 serum Anatomy 0.000 description 2
208000000587 small cell lung carcinoma Diseases 0.000 description 2
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
159000000000 sodium salts Chemical class 0.000 description 2
ALPWRKFXEOAUDR-GKEJWYBXSA-M sodium;[(2r)-2,3-di(octadecanoyloxy)propyl] hydrogen phosphate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)([O-])=O)OC(=O)CCCCCCCCCCCCCCCCC ALPWRKFXEOAUDR-GKEJWYBXSA-M 0.000 description 2
NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
238000010911 splenectomy Methods 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
150000003432 sterols Chemical class 0.000 description 2
235000003702 sterols Nutrition 0.000 description 2
238000003860 storage Methods 0.000 description 2
238000010254 subcutaneous injection Methods 0.000 description 2
239000007929 subcutaneous injection Substances 0.000 description 2
125000005017 substituted alkenyl group Chemical group 0.000 description 2
125000004426 substituted alkynyl group Chemical group 0.000 description 2
125000003107 substituted aryl group Chemical group 0.000 description 2
125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
239000004094 surface-active agent Substances 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
238000013268 sustained release Methods 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
RXUZRBQIVIUOLJ-UHFFFAOYSA-N tert-butyl n-[3-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propylamino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNCCCNC(=O)OC(C)(C)C RXUZRBQIVIUOLJ-UHFFFAOYSA-N 0.000 description 2
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 2
239000005451 thionucleotide Substances 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
150000004670 unsaturated fatty acids Chemical class 0.000 description 2
235000021122 unsaturated fatty acids Nutrition 0.000 description 2
229960001134 von willebrand factor Drugs 0.000 description 2
SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
VBZSMBBOZFITID-FRWASNMLSA-N (2-aminoethoxy)[(2r)-2,3-bis[(13z)-docos-13-enoyloxy]propoxy]phosphinic acid Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCC\C=C/CCCCCCCC VBZSMBBOZFITID-FRWASNMLSA-N 0.000 description 1
YKIOPDIXYAUOFN-YACUFSJGSA-N (2-{[(2r)-2,3-bis(icosanoyloxy)propyl phosphonato]oxy}ethyl)trimethylazanium Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCCCCCC YKIOPDIXYAUOFN-YACUFSJGSA-N 0.000 description 1
SDEURMLKLAEUAY-JFSPZUDSSA-N (2-{[(2r)-2,3-bis[(13z)-docos-13-enoyloxy]propyl phosphonato]oxy}ethyl)trimethylazanium Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCC\C=C/CCCCCCCC SDEURMLKLAEUAY-JFSPZUDSSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
OPCHFPHZPIURNA-MFERNQICSA-N (2s)-2,5-bis(3-aminopropylamino)-n-[2-(dioctadecylamino)acetyl]pentanamide Chemical compound CCCCCCCCCCCCCCCCCCN(CC(=O)NC(=O)[C@H](CCCNCCCN)NCCCN)CCCCCCCCCCCCCCCCCC OPCHFPHZPIURNA-MFERNQICSA-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
ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 description 1
UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
229930182837 (R)-adrenaline Natural products 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
LZLVZIFMYXDKCN-QJWFYWCHSA-N 1,2-di-O-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=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 LZLVZIFMYXDKCN-QJWFYWCHSA-N 0.000 description 1
MWRBNPKJOOWZPW-GPADLTIESA-N 1,2-di-[(9E)-octadecenoyl]-sn-glycero-3-phosphoethanolamine Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCC\C=C\CCCCCCCC MWRBNPKJOOWZPW-GPADLTIESA-N 0.000 description 1
229940083937 1,2-diarachidoyl-sn-glycero-3-phosphocholine Drugs 0.000 description 1
DSNRWDQKZIEDDB-SQYFZQSCSA-N 1,2-dioleoyl-sn-glycero-3-phospho-(1'-sn-glycerol) Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@@H](O)CO)OC(=O)CCCCCCC\C=C/CCCCCCCC DSNRWDQKZIEDDB-SQYFZQSCSA-N 0.000 description 1
FGODUFHTWYYOOB-UHFFFAOYSA-N 1,3-diaminopropan-2-yl dihydrogen phosphate Chemical compound NCC(CN)OP(O)(O)=O FGODUFHTWYYOOB-UHFFFAOYSA-N 0.000 description 1
FJLUATLTXUNBOT-UHFFFAOYSA-N 1-Hexadecylamine Chemical compound CCCCCCCCCCCCCCCCN FJLUATLTXUNBOT-UHFFFAOYSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-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
BYSIMVBIJVBVPA-RRHRGVEJSA-N 1-stearoyl-2-palmitoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC BYSIMVBIJVBVPA-RRHRGVEJSA-N 0.000 description 1
RBZRMBCLZMEYEH-UHFFFAOYSA-N 1h-pyrazol-1-ium-1-carboximidamide;chloride Chemical compound Cl.NC(=N)N1C=CC=N1 RBZRMBCLZMEYEH-UHFFFAOYSA-N 0.000 description 1
KWVJHCQQUFDPLU-YEUCEMRASA-N 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KWVJHCQQUFDPLU-YEUCEMRASA-N 0.000 description 1
WALUVDCNGPQPOD-UHFFFAOYSA-M 2,3-di(tetradecoxy)propyl-(2-hydroxyethyl)-dimethylazanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCOCC(C[N+](C)(C)CCO)OCCCCCCCCCCCCCC WALUVDCNGPQPOD-UHFFFAOYSA-M 0.000 description 1
LAGUSEHJTGJJRJ-UHFFFAOYSA-N 2,5-bis(3-aminopropylamino)-n-[2-(dioctadecylamino)-2-oxoethyl]pentanamide Chemical compound CCCCCCCCCCCCCCCCCCN(C(=O)CNC(=O)C(CCCNCCCN)NCCCN)CCCCCCCCCCCCCCCCCC LAGUSEHJTGJJRJ-UHFFFAOYSA-N 0.000 description 1
RGNOTKMIMZMNRX-XVFCMESISA-N 2-amino-1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-4-one Chemical compound NC1=NC(=O)C=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 RGNOTKMIMZMNRX-XVFCMESISA-N 0.000 description 1
MSWZFWKMSRAUBD-GASJEMHNSA-N 2-amino-2-deoxy-D-galactopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O MSWZFWKMSRAUBD-GASJEMHNSA-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
JCCCMAAJYSNBPR-UHFFFAOYSA-N 2-ethylthiophene Chemical group CCC1=CC=CS1 JCCCMAAJYSNBPR-UHFFFAOYSA-N 0.000 description 1
HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
KUQZVISZELWDNZ-UHFFFAOYSA-N 3-aminopropyl dihydrogen phosphate Chemical compound NCCCOP(O)(O)=O KUQZVISZELWDNZ-UHFFFAOYSA-N 0.000 description 1
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 1
DQQNMIPXXNPGCV-UHFFFAOYSA-N 3-hexyne Chemical compound CCC#CCC DQQNMIPXXNPGCV-UHFFFAOYSA-N 0.000 description 1
HYCSHFLKPSMPGO-UHFFFAOYSA-N 3-hydroxypropyl dihydrogen phosphate Chemical compound OCCCOP(O)(O)=O HYCSHFLKPSMPGO-UHFFFAOYSA-N 0.000 description 1
RFSKGCVUDQRZSD-UHFFFAOYSA-N 3-methoxythiophene Chemical group COC=1C=CSC=1 RFSKGCVUDQRZSD-UHFFFAOYSA-N 0.000 description 1
WHNPOQXWAMXPTA-UHFFFAOYSA-N 3-methylbut-2-enamide Chemical compound CC(C)=CC(N)=O WHNPOQXWAMXPTA-UHFFFAOYSA-N 0.000 description 1
ZLOIGESWDJYCTF-UHFFFAOYSA-N 4-Thiouridine Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-UHFFFAOYSA-N 0.000 description 1
HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
ZLOIGESWDJYCTF-XVFCMESISA-N 4-thiouridine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=S)C=C1 ZLOIGESWDJYCTF-XVFCMESISA-N 0.000 description 1
HTMGQIXFZMZZKD-UHFFFAOYSA-N 5,6,7,8-tetrahydroisoquinoline Chemical compound N1=CC=C2CCCCC2=C1 HTMGQIXFZMZZKD-UHFFFAOYSA-N 0.000 description 1
LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical group BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical group IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 1
LIFHMKCDDVTICL-UHFFFAOYSA-N 6-(chloromethyl)phenanthridine Chemical compound C1=CC=C2C(CCl)=NC3=CC=CC=C3C2=C1 LIFHMKCDDVTICL-UHFFFAOYSA-N 0.000 description 1
XYVLZAYJHCECPN-UHFFFAOYSA-N 6-aminohexyl phosphate Chemical compound NCCCCCCOP(O)(O)=O XYVLZAYJHCECPN-UHFFFAOYSA-N 0.000 description 1
XYVLZAYJHCECPN-UHFFFAOYSA-L 6-aminohexyl phosphate Chemical compound NCCCCCCOP([O-])([O-])=O XYVLZAYJHCECPN-UHFFFAOYSA-L 0.000 description 1
BZTDTCNHAFUJOG-UHFFFAOYSA-N 6-carboxyfluorescein Chemical compound C12=CC=C(O)C=C2OC2=CC(O)=CC=C2C11OC(=O)C2=CC=C(C(=O)O)C=C21 BZTDTCNHAFUJOG-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
208000035657 Abasia Diseases 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
208000023275 Autoimmune disease Diseases 0.000 description 1
108091012583 BCL2 Proteins 0.000 description 1
101150017888 Bcl2 gene Proteins 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
0 CC(*)(*)C(*)(*1C2C1)C2(*)N(*)CCC* Chemical compound CC(*)(*)C(*)(*1C2C1)C2(*)N(*)CCC* 0.000 description 1
SMCVBZLSHOVSKQ-UPWUHKKVSA-N CC(C)CCC[C@@H](C)[C@@H](CC1)[C@@](C)(CC2)[C@@H]1[C@H]1[C@H]2[C@@](C)(CC[C@@H](C2)OC(OCCN(CCCNC(N)=N)CCCNC(N)=N)=O)C2=CC1 Chemical compound CC(C)CCC[C@@H](C)[C@@H](CC1)[C@@](C)(CC2)[C@@H]1[C@H]1[C@H]2[C@@](C)(CC[C@@H](C2)OC(OCCN(CCCNC(N)=N)CCCNC(N)=N)=O)C2=CC1 SMCVBZLSHOVSKQ-UPWUHKKVSA-N 0.000 description 1
RBGCWNFXPQALRC-UHFFFAOYSA-N CN(CCCN(CCCCN(CCC(N(C(CCCCCCCCCCCCCCC)=O)C(CCCCCCCCCCCCCCC)=O)(C(CCCCCCCCCCCCCCC)=O)C(CCCCCCCCCCCCCCC)=O)C)C)C Chemical compound CN(CCCN(CCCCN(CCC(N(C(CCCCCCCCCCCCCCC)=O)C(CCCCCCCCCCCCCCC)=O)(C(CCCCCCCCCCCCCCC)=O)C(CCCCCCCCCCCCCCC)=O)C)C)C RBGCWNFXPQALRC-UHFFFAOYSA-N 0.000 description 1
NFIDGYIHSCPMMK-SDLHUVDUSA-N CN(CCCN(CCCCN(CCC(N(CCCCCCCC\C=C/CCCCCCCC)CCCCCCCC\C=C/CCCCCCCC)(CCCCCCCC\C=C/CCCCCCCC)CCCCCCCC\C=C/CCCCCCCC)C)C)C Chemical compound CN(CCCN(CCCCN(CCC(N(CCCCCCCC\C=C/CCCCCCCC)CCCCCCCC\C=C/CCCCCCCC)(CCCCCCCC\C=C/CCCCCCCC)CCCCCCCC\C=C/CCCCCCCC)C)C)C NFIDGYIHSCPMMK-SDLHUVDUSA-N 0.000 description 1
ZZDFKFPJTXZAAK-UHFFFAOYSA-N CN(CCCN(CCCCN(CCCN(C)C)CCCCCCCCC=C/CCCCCCCC)CCCCCCCCC=C/CCCCCCCC)C Chemical compound CN(CCCN(CCCCN(CCCN(C)C)CCCCCCCCC=C/CCCCCCCC)CCCCCCCCC=C/CCCCCCCC)C ZZDFKFPJTXZAAK-UHFFFAOYSA-N 0.000 description 1
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
108020004705 Codon Proteins 0.000 description 1
108020004635 Complementary DNA Proteins 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
AERBNCYCJBRYDG-UHFFFAOYSA-N D-ribo-phytosphingosine Natural products CCCCCCCCCCCCCCC(O)C(O)C(N)CO AERBNCYCJBRYDG-UHFFFAOYSA-N 0.000 description 1
238000002965 ELISA Methods 0.000 description 1
241000792859 Enema Species 0.000 description 1
108700039887 Essential Genes Proteins 0.000 description 1
102100035290 Fibroblast growth factor 13 Human genes 0.000 description 1
108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
102400000321 Glucagon Human genes 0.000 description 1
108060003199 Glucagon Proteins 0.000 description 1
108010051696 Growth Hormone Proteins 0.000 description 1
241000282412 Homo Species 0.000 description 1
101100501692 Homo sapiens ERBB3 gene Proteins 0.000 description 1
101001066129 Homo sapiens Glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
102000004877 Insulin Human genes 0.000 description 1
108090001061 Insulin Proteins 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
108090001090 Lectins Proteins 0.000 description 1
102000004856 Lectins Human genes 0.000 description 1
239000000232 Lipid Bilayer Substances 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
108010007013 Melanocyte-Stimulating Hormones Proteins 0.000 description 1
206010027457 Metastases to liver Diseases 0.000 description 1
101150015254 Moe gene Proteins 0.000 description 1
208000003445 Mouth Neoplasms Diseases 0.000 description 1
241000699660 Mus musculus 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
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 1
102000015336 Nerve Growth Factor Human genes 0.000 description 1
108010077641 Nogo Proteins Proteins 0.000 description 1
238000000636 Northern blotting Methods 0.000 description 1
REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
239000004952 Polyamide Substances 0.000 description 1
229920000954 Polyglycolide Polymers 0.000 description 1
239000004372 Polyvinyl alcohol Substances 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
238000011529 RT qPCR Methods 0.000 description 1
102100029831 Reticulon-4 Human genes 0.000 description 1
208000000453 Skin Neoplasms Diseases 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
102000005157 Somatostatin Human genes 0.000 description 1
108010056088 Somatostatin Proteins 0.000 description 1
102100038803 Somatotropin Human genes 0.000 description 1
108091027076 Spiegelmer Proteins 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
101150084279 TM gene Proteins 0.000 description 1
AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
102000004338 Transferrin Human genes 0.000 description 1
108090000901 Transferrin Proteins 0.000 description 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical group NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
229930003316 Vitamin D Natural products 0.000 description 1
QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
MMWCIQZXVOZEGG-HOZKJCLWSA-N [(1S,2R,3S,4S,5R,6S)-2,3,5-trihydroxy-4,6-diphosphonooxycyclohexyl] dihydrogen phosphate Chemical compound O[C@H]1[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](O)[C@H]1OP(O)(O)=O MMWCIQZXVOZEGG-HOZKJCLWSA-N 0.000 description 1
JCABVIFDXFFRMT-DIPNUNPCSA-N [(2r)-1-[ethoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] octadec-9-enoate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC)OC(=O)CCCCCCCC=CCCCCCCCC JCABVIFDXFFRMT-DIPNUNPCSA-N 0.000 description 1
JYJIYAOIKUDVPZ-XDLWQMJLSA-N [(2r)-3-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-2-[(z)-docos-13-enoyl]oxypropyl] (z)-docos-13-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCC\C=C/CCCCCCCC JYJIYAOIKUDVPZ-XDLWQMJLSA-N 0.000 description 1
HIHOWBSBBDRPDW-PTHRTHQKSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] n-[2-(dimethylamino)ethyl]carbamate Chemical compound C1C=C2C[C@@H](OC(=O)NCCN(C)C)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 HIHOWBSBBDRPDW-PTHRTHQKSA-N 0.000 description 1
ISXSJGHXHUZXNF-LXZPIJOJSA-N [(3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-yl] n-[2-(dimethylamino)ethyl]carbamate;hydrochloride Chemical compound Cl.C1C=C2C[C@@H](OC(=O)NCCN(C)C)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 ISXSJGHXHUZXNF-LXZPIJOJSA-N 0.000 description 1
FGYYWCMRFGLJOB-MQWKRIRWSA-N [2,3-dihydroxypropoxy(hydroxy)phosphoryl] (2s)-2,6-diaminohexanoate Chemical compound NCCCC[C@H](N)C(=O)OP(O)(=O)OCC(O)CO FGYYWCMRFGLJOB-MQWKRIRWSA-N 0.000 description 1
HMNZFMSWFCAGGW-XPWSMXQVSA-N [3-[hydroxy(2-hydroxyethoxy)phosphoryl]oxy-2-[(e)-octadec-9-enoyl]oxypropyl] (e)-octadec-9-enoate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(COP(O)(=O)OCCO)OC(=O)CCCCCCC\C=C\CCCCCCCC HMNZFMSWFCAGGW-XPWSMXQVSA-N 0.000 description 1
238000002835 absorbance Methods 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
VUBTYKDZOQNADH-UHFFFAOYSA-N acetyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)=O VUBTYKDZOQNADH-UHFFFAOYSA-N 0.000 description 1
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
229960004373 acetylcholine Drugs 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
125000002015 acyclic group Chemical group 0.000 description 1
125000004442 acylamino group Chemical group 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
229940040563 agaric acid Drugs 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000002877 alkyl aryl group Chemical group 0.000 description 1
125000005093 alkyl carbonyl alkyl group Chemical group 0.000 description 1
125000004448 alkyl carbonyl group Chemical group 0.000 description 1
SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
150000001414 amino alcohols Chemical class 0.000 description 1
125000005021 aminoalkenyl group Chemical group 0.000 description 1
125000004103 aminoalkyl group Chemical group 0.000 description 1
125000005014 aminoalkynyl group Chemical group 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
229940124650 anti-cancer therapies Drugs 0.000 description 1
238000011319 anticancer therapy Methods 0.000 description 1
102000025171 antigen binding proteins Human genes 0.000 description 1
108091000831 antigen binding proteins Proteins 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
230000006907 apoptotic process Effects 0.000 description 1
229920006187 aquazol Polymers 0.000 description 1
239000012062 aqueous buffer Substances 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
125000004104 aryloxy group Chemical group 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
239000003613 bile acid Substances 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
210000000481 breast Anatomy 0.000 description 1
239000012267 brine Substances 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000004067 bulking agent Substances 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
238000010804 cDNA synthesis Methods 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000004202 carbamide Chemical group 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
125000000837 carbohydrate group Chemical group 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
125000005243 carbonyl alkyl group Chemical group 0.000 description 1
125000005019 carboxyalkenyl group Chemical group 0.000 description 1
125000004181 carboxyalkyl group Chemical group 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
150000001735 carboxylic acids Chemical group 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
230000021164 cell adhesion Effects 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
230000019522 cellular metabolic process Effects 0.000 description 1
150000001783 ceramides Chemical class 0.000 description 1
238000007385 chemical modification Methods 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
238000002648 combination therapy Methods 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
230000021615 conjugation Effects 0.000 description 1
229920001577 copolymer Polymers 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
208000014446 corneal intraepithelial dyskeratosis-palmoplantar hyperkeratosis-laryngeal dyskeratosis syndrome Diseases 0.000 description 1
229940099112 cornstarch Drugs 0.000 description 1
230000000875 corresponding effect Effects 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
239000012043 crude product Substances 0.000 description 1
125000006165 cyclic alkyl group Chemical group 0.000 description 1
108010045325 cyclic arginine-glycine-aspartic acid peptide Proteins 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000002188 cycloheptatrienyl group Chemical group C1(=CC=CC=CC1)* 0.000 description 1
125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
210000000805 cytoplasm Anatomy 0.000 description 1
230000007711 cytoplasmic localization Effects 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
230000034994 death Effects 0.000 description 1
231100000517 death Toxicity 0.000 description 1
230000007423 decrease Effects 0.000 description 1
208000033921 delayed sleep phase type circadian rhythm sleep disease Diseases 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
239000003599 detergent Substances 0.000 description 1
239000000032 diagnostic agent Substances 0.000 description 1
229940039227 diagnostic agent Drugs 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
XRWMGCFJVKDVMD-UHFFFAOYSA-M didodecyl(dimethyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCC XRWMGCFJVKDVMD-UHFFFAOYSA-M 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
OTKJDMGTUTTYMP-UHFFFAOYSA-N dihydrosphingosine Natural products CCCCCCCCCCCCCCCC(O)C(N)CO OTKJDMGTUTTYMP-UHFFFAOYSA-N 0.000 description 1
PSLWZOIUBRXAQW-UHFFFAOYSA-M dimethyl(dioctadecyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC PSLWZOIUBRXAQW-UHFFFAOYSA-M 0.000 description 1
UAKOZKUVZRMOFN-JDVCJPALSA-M dimethyl-bis[(z)-octadec-9-enyl]azanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC[N+](C)(C)CCCCCCCC\C=C/CCCCCCCC UAKOZKUVZRMOFN-JDVCJPALSA-M 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
150000002019 disulfides Chemical class 0.000 description 1
NAGJZTKCGNOGPW-UHFFFAOYSA-N dithiophosphoric acid Chemical class OP(O)(S)=S NAGJZTKCGNOGPW-UHFFFAOYSA-N 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
JRBPAEWTRLWTQC-UHFFFAOYSA-N dodecylamine Chemical compound CCCCCCCCCCCCN JRBPAEWTRLWTQC-UHFFFAOYSA-N 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000003651 drinking water Substances 0.000 description 1
235000020188 drinking water Nutrition 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
238000009509 drug development Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Natural products C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
239000007920 enema Substances 0.000 description 1
229940079360 enema for constipation Drugs 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
230000009088 enzymatic function Effects 0.000 description 1
229960005139 epinephrine Drugs 0.000 description 1
229940011871 estrogen Drugs 0.000 description 1
239000000262 estrogen Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
150000002190 fatty acyls Chemical group 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
238000000799 fluorescence microscopy Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
229940014144 folate Drugs 0.000 description 1
125000003929 folic acid group Chemical group 0.000 description 1
230000037406 food intake Effects 0.000 description 1
239000012634 fragment Substances 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
229930182830 galactose Natural products 0.000 description 1
229960003692 gamma aminobutyric acid Drugs 0.000 description 1
BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
150000002270 gangliosides Chemical class 0.000 description 1
239000000499 gel Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000001476 gene delivery Methods 0.000 description 1
238000003633 gene expression assay Methods 0.000 description 1
230000030279 gene silencing Effects 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
229960004666 glucagon Drugs 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
229940049906 glutamate Drugs 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
JEJLGIQLPYYGEE-UHFFFAOYSA-N glycerol dipalmitate Natural products CCCCCCCCCCCCCCCC(=O)OCC(CO)OC(=O)CCCCCCCCCCCCCCC JEJLGIQLPYYGEE-UHFFFAOYSA-N 0.000 description 1
239000008202 granule composition Substances 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
239000000122 growth hormone Substances 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000004405 heteroalkoxy group Chemical group 0.000 description 1
125000005553 heteroaryloxy group Chemical group 0.000 description 1
PHNWGDTYCJFUGZ-UHFFFAOYSA-L hexyl phosphate Chemical compound CCCCCCOP([O-])([O-])=O PHNWGDTYCJFUGZ-UHFFFAOYSA-L 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
102000047486 human GAPDH Human genes 0.000 description 1
229960000890 hydrocortisone Drugs 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
229920001600 hydrophobic polymer Polymers 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
125000005020 hydroxyalkenyl group Chemical group 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
125000005016 hydroxyalkynyl group Chemical group 0.000 description 1
235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
230000028993 immune response Effects 0.000 description 1
230000009851 immunogenic response Effects 0.000 description 1
238000001114 immunoprecipitation Methods 0.000 description 1
238000002513 implantation Methods 0.000 description 1
230000006872 improvement Effects 0.000 description 1
238000007901 in situ hybridization Methods 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
238000001802 infusion Methods 0.000 description 1
229940125396 insulin Drugs 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
230000002601 intratumoral effect Effects 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
230000002147 killing effect Effects 0.000 description 1
239000008101 lactose Substances 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
239000002523 lectin Substances 0.000 description 1
208000032839 leukemia Diseases 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
125000005644 linolenyl group Chemical group 0.000 description 1
208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
LWXVCCOAQYNXNX-UHFFFAOYSA-N lithium hypochlorite Chemical compound [Li+].Cl[O-] LWXVCCOAQYNXNX-UHFFFAOYSA-N 0.000 description 1
208000019423 liver disease Diseases 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
229920001427 mPEG Polymers 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
230000003211 malignant effect Effects 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
125000005358 mercaptoalkyl group Chemical group 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical compound CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
CAAULPUQFIIOTL-UHFFFAOYSA-N methyl dihydrogen phosphate Chemical group COP(O)(O)=O CAAULPUQFIIOTL-UHFFFAOYSA-N 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical class CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
125000004372 methylthioethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])* 0.000 description 1
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
239000007758 minimum essential medium Substances 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
210000004877 mucosa Anatomy 0.000 description 1
UNAFTICPPXVTTN-UHFFFAOYSA-N n-dodecyldodecan-1-amine;hydrobromide Chemical compound [Br-].CCCCCCCCCCCC[NH2+]CCCCCCCCCCCC UNAFTICPPXVTTN-UHFFFAOYSA-N 0.000 description 1
239000006199 nebulizer Substances 0.000 description 1
230000001613 neoplastic effect Effects 0.000 description 1
239000002858 neurotransmitter agent Substances 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
229960002748 norepinephrine Drugs 0.000 description 1
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
230000004942 nuclear accumulation Effects 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
150000003833 nucleoside derivatives Chemical class 0.000 description 1
238000011580 nude mouse model Methods 0.000 description 1
125000001117 oleyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
229940000673 orphan drug Drugs 0.000 description 1
239000002859 orphan drug Substances 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
150000002924 oxiranes Chemical class 0.000 description 1
125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000006072 paste Substances 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
238000012247 phenotypical assay Methods 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
150000008103 phosphatidic acids Chemical class 0.000 description 1
125000001095 phosphatidyl group Chemical group 0.000 description 1
UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
150000008298 phosphoramidates Chemical class 0.000 description 1
AERBNCYCJBRYDG-KSZLIROESA-N phytosphingosine Chemical compound CCCCCCCCCCCCCC[C@@H](O)[C@@H](O)[C@@H](N)CO AERBNCYCJBRYDG-KSZLIROESA-N 0.000 description 1
229940033329 phytosphingosine Drugs 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920000233 poly(alkylene oxides) Polymers 0.000 description 1
229920000747 poly(lactic acid) Polymers 0.000 description 1
229920002946 poly[2-(methacryloxy)ethyl phosphorylcholine] polymer Polymers 0.000 description 1
229920000058 polyacrylate Polymers 0.000 description 1
229920002647 polyamide Polymers 0.000 description 1
229920000768 polyamine Polymers 0.000 description 1
229920000570 polyether Polymers 0.000 description 1
239000004633 polyglycolic acid Substances 0.000 description 1
239000004626 polylactic acid Substances 0.000 description 1
229920001184 polypeptide Polymers 0.000 description 1
229920002451 polyvinyl alcohol Polymers 0.000 description 1
229920001592 potato starch Polymers 0.000 description 1
229940116317 potato starch Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
230000002028 premature Effects 0.000 description 1
150000003141 primary amines Chemical group 0.000 description 1
230000009443 proangiogenesis Effects 0.000 description 1
230000008569 process Effects 0.000 description 1
229960003387 progesterone Drugs 0.000 description 1
239000000186 progesterone Substances 0.000 description 1
230000009682 proliferation pathway Effects 0.000 description 1
GGHDAUPFEBTORZ-UHFFFAOYSA-N propane-1,1-diamine Chemical compound CCC(N)N GGHDAUPFEBTORZ-UHFFFAOYSA-N 0.000 description 1
239000003380 propellant Substances 0.000 description 1
MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
210000002307 prostate Anatomy 0.000 description 1
208000023958 prostate neoplasm Diseases 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
230000002685 pulmonary effect Effects 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
239000011677 pyridoxine Chemical group 0.000 description 1
235000008160 pyridoxine Nutrition 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
239000002510 pyrogen Substances 0.000 description 1
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
238000007348 radical reaction Methods 0.000 description 1
238000003753 real-time PCR Methods 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
229930002330 retinoic acid Natural products 0.000 description 1
229940100486 rice starch Drugs 0.000 description 1
WBHHMMIMDMUBKC-QJWNTBNXSA-M ricinoleate Chemical compound CCCCCC[C@@H](O)C\C=C/CCCCCCCC([O-])=O WBHHMMIMDMUBKC-QJWNTBNXSA-M 0.000 description 1
229940066675 ricinoleate Drugs 0.000 description 1
229920002477 rna polymer Polymers 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
150000004756 silanes Chemical class 0.000 description 1
238000004513 sizing Methods 0.000 description 1
201000000849 skin cancer Diseases 0.000 description 1
239000002002 slurry Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
FGGPAWQCCGEWTJ-UHFFFAOYSA-M sodium;2,3-bis(sulfanyl)propane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CC(S)CS FGGPAWQCCGEWTJ-UHFFFAOYSA-M 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
229960000553 somatostatin Drugs 0.000 description 1
229940063675 spermine Drugs 0.000 description 1
OTKJDMGTUTTYMP-ZWKOTPCHSA-N sphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@@H](N)CO OTKJDMGTUTTYMP-ZWKOTPCHSA-N 0.000 description 1
210000000952 spleen Anatomy 0.000 description 1
239000007921 spray Substances 0.000 description 1
230000000087 stabilizing effect Effects 0.000 description 1
125000003696 stearoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000003270 steroid hormone Substances 0.000 description 1
230000003637 steroidlike Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
238000009495 sugar coating Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000012385 systemic delivery Methods 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
238000009121 systemic therapy Methods 0.000 description 1
QQWYQAQQADNEIC-UHFFFAOYSA-N tert-butyl [[cyano(phenyl)methylidene]amino] carbonate Chemical compound CC(C)(C)OC(=O)ON=C(C#N)C1=CC=CC=C1 QQWYQAQQADNEIC-UHFFFAOYSA-N 0.000 description 1
CSOJECDGWHHWRS-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylcarbamothioyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(=S)NC(=O)OC(C)(C)C CSOJECDGWHHWRS-UHFFFAOYSA-N 0.000 description 1
IGSFMHYSWZUENI-UHFFFAOYSA-N tert-butyl n-[amino(pyrazol-1-yl)methylidene]carbamate Chemical compound CC(C)(C)OC(=O)N=C(N)N1C=CC=N1 IGSFMHYSWZUENI-UHFFFAOYSA-N 0.000 description 1
229960003604 testosterone Drugs 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
239000005495 thyroid hormone Substances 0.000 description 1
229940036555 thyroid hormone Drugs 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
239000012581 transferrin Substances 0.000 description 1
238000013519 translation Methods 0.000 description 1
210000003956 transport vesicle Anatomy 0.000 description 1
229960001727 tretinoin Drugs 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
AVBGNFCMKJOFIN-UHFFFAOYSA-N triethylammonium acetate Chemical compound CC(O)=O.CCN(CC)CC AVBGNFCMKJOFIN-UHFFFAOYSA-N 0.000 description 1
238000002371 ultraviolet--visible spectrum Methods 0.000 description 1
230000003827 upregulation Effects 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
235000019166 vitamin D Nutrition 0.000 description 1
239000011710 vitamin D Substances 0.000 description 1
150000003710 vitamin D derivatives Chemical class 0.000 description 1
229940011671 vitamin b6 Drugs 0.000 description 1
229940046008 vitamin d Drugs 0.000 description 1
108010047303 von Willebrand Factor Proteins 0.000 description 1
102100036537 von Willebrand factor Human genes 0.000 description 1
238000001262 western blot Methods 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1
OIWCYIUQAVBPGV-DAQGAKHBSA-N {1-O-hexadecanoyl-2-O-[(Z)-octadec-9-enoyl]-sn-glycero-3-phospho}serine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC OIWCYIUQAVBPGV-DAQGAKHBSA-N 0.000 description 1
SFVVQRJOGUKCEG-OPQSFPLASA-N β-MSH Chemical compound C1C[C@@H](O)[C@H]2C(COC(=O)[C@@](O)([C@@H](C)O)C(C)C)=CCN21 SFVVQRJOGUKCEG-OPQSFPLASA-N 0.000 description 1