TW202403045A - 反義誘導之酸性α-葡萄苷酶中的外顯子2包含 - Google Patents

Info

Publication number

TW202403045A

TW202403045A TW112123102A TW112123102A TW202403045A TW 202403045 A TW202403045 A TW 202403045A TW 112123102 A TW112123102 A TW 112123102A TW 112123102 A TW112123102 A TW 112123102A TW 202403045 A TW202403045 A TW 202403045A

Authority

TW

Taiwan

Prior art keywords

seq

series

ggg

cxg

ccc

Prior art date

2015-02-27

Links

• Espacenet
• Global Dossier
• Discuss

• 230000000692 anti-sense effect Effects 0.000 title abstract description 592
• 239000002253 acid Substances 0.000 title abstract description 22
• 108010028144 alpha-Glucosidases Proteins 0.000 title abstract description 15
• 102100024295 Maltase-glucoamylase Human genes 0.000 title 1
• 206010053185 Glycogen storage disease type II Diseases 0.000 claims abstract description 84
• 201000004502 glycogen storage disease II Diseases 0.000 claims abstract description 80
• 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 claims abstract description 76
• 238000011282 treatment Methods 0.000 claims abstract description 38
• 150000001875 compounds Chemical class 0.000 claims description 184
• ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 122
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 claims description 121
• -1 4-methoxytrityl Chemical group 0.000 claims description 77
• 239000003795 chemical substances by application Substances 0.000 claims description 74
• 229910052739 hydrogen Inorganic materials 0.000 claims description 74
• 229910052799 carbon Inorganic materials 0.000 claims description 73
• 229940035893 uracil Drugs 0.000 claims description 61
• 229940113082 thymine Drugs 0.000 claims description 60
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 46
• 150000003839 salts Chemical class 0.000 claims description 43
• 239000008194 pharmaceutical composition Substances 0.000 claims description 35
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 35
• 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 claims description 34
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 25
• 125000000217 alkyl group Chemical group 0.000 claims description 24
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
• 125000002252 acyl group Chemical group 0.000 claims description 20
• 108010051109 Cell-Penetrating Peptides Proteins 0.000 claims description 15
• 102000020313 Cell-Penetrating Peptides Human genes 0.000 claims description 15
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 15
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
• 239000003937 drug carrier Substances 0.000 claims description 12
• 238000002360 preparation method Methods 0.000 claims description 12
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 8
• 125000005313 fatty acid group Chemical group 0.000 claims 2
• 238000004519 manufacturing process Methods 0.000 claims 2
• 238000000034 method Methods 0.000 abstract description 97
• 108090000623 proteins and genes Proteins 0.000 abstract description 80
• 239000000203 mixture Substances 0.000 abstract description 49
• 102000004169 proteins and genes Human genes 0.000 abstract description 49
• 101150115151 GAA gene Proteins 0.000 abstract description 13
• 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 abstract description 12
• 230000001939 inductive effect Effects 0.000 abstract description 4
• 208000007345 glycogen storage disease Diseases 0.000 abstract description 3
• 108020004414 DNA Proteins 0.000 description 387
• ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 205
• 210000004027 cell Anatomy 0.000 description 131
• 108020004999 messenger RNA Proteins 0.000 description 97
• 239000002585 base Substances 0.000 description 79
• 125000003729 nucleotide group Chemical group 0.000 description 73
• 239000002773 nucleotide Substances 0.000 description 71
• 230000000694 effects Effects 0.000 description 68
• 102000004190 Enzymes Human genes 0.000 description 54
• 108090000790 Enzymes Proteins 0.000 description 54
• 229940088598 enzyme Drugs 0.000 description 54
• 230000000295 complement effect Effects 0.000 description 52
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 45
• 230000008685 targeting Effects 0.000 description 39
• 235000018102 proteins Nutrition 0.000 description 37
• 108091093037 Peptide nucleic acid Proteins 0.000 description 34
• 125000002091 cationic group Chemical group 0.000 description 31
• 150000007523 nucleic acids Chemical class 0.000 description 31
• 101001018026 Homo sapiens Lysosomal alpha-glucosidase Proteins 0.000 description 29
• 102000045921 human GAA Human genes 0.000 description 29
• 102000039446 nucleic acids Human genes 0.000 description 29
• 108020004707 nucleic acids Proteins 0.000 description 29
• 239000002502 liposome Substances 0.000 description 28
• 108090000765 processed proteins & peptides Proteins 0.000 description 27
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
• 239000012634 fragment Substances 0.000 description 26
• 230000001965 increasing effect Effects 0.000 description 26
• 125000005647 linker group Chemical group 0.000 description 26
• 108091034117 Oligonucleotide Proteins 0.000 description 24
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
• 210000001519 tissue Anatomy 0.000 description 24
• 229910052757 nitrogen Inorganic materials 0.000 description 23
• 239000003814 drug Substances 0.000 description 22
• 125000006239 protecting group Chemical group 0.000 description 22
• 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 21
• 230000027455 binding Effects 0.000 description 21
• 238000009472 formulation Methods 0.000 description 21
• 230000035772 mutation Effects 0.000 description 21
• 201000010099 disease Diseases 0.000 description 19
• 239000000126 substance Substances 0.000 description 19
• 241000282414 Homo sapiens Species 0.000 description 18
• 210000002950 fibroblast Anatomy 0.000 description 18
• 238000012986 modification Methods 0.000 description 18
• 239000002243 precursor Substances 0.000 description 18
• 230000004048 modification Effects 0.000 description 17
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 17
• 101710163270 Nuclease Proteins 0.000 description 16
• 125000003118 aryl group Chemical group 0.000 description 16
• 230000015572 biosynthetic process Effects 0.000 description 16
• 239000006166 lysate Substances 0.000 description 16
• RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 14
• 238000003786 synthesis reaction Methods 0.000 description 14
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
• 102000016679 alpha-Glucosidases Human genes 0.000 description 12
• 229940024606 amino acid Drugs 0.000 description 12
• 229940079593 drug Drugs 0.000 description 12
• 238000009585 enzyme analysis Methods 0.000 description 12
• FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 12
• 238000001727 in vivo Methods 0.000 description 12
• 125000004433 nitrogen atom Chemical group N* 0.000 description 12
• 108091033319 polynucleotide Proteins 0.000 description 12
• 102000040430 polynucleotide Human genes 0.000 description 12
• 239000002157 polynucleotide Substances 0.000 description 12
• 235000000346 sugar Nutrition 0.000 description 12
• 229920002527 Glycogen Polymers 0.000 description 11
• JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 11
• 238000009825 accumulation Methods 0.000 description 11
• 235000001014 amino acid Nutrition 0.000 description 11
• 238000006243 chemical reaction Methods 0.000 description 11
• 229940096919 glycogen Drugs 0.000 description 11
• 230000035515 penetration Effects 0.000 description 11
• 150000001413 amino acids Chemical class 0.000 description 10
• 239000003623 enhancer Substances 0.000 description 10
• 125000004437 phosphorous atom Chemical group 0.000 description 10
• 229910052698 phosphorus Inorganic materials 0.000 description 10
• 238000003757 reverse transcription PCR Methods 0.000 description 10
• 208000024891 symptom Diseases 0.000 description 10
• 239000004475 Arginine Substances 0.000 description 9
• 238000004458 analytical method Methods 0.000 description 9
• 239000000074 antisense oligonucleotide Substances 0.000 description 9
• 238000012230 antisense oligonucleotides Methods 0.000 description 9
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 9
• 239000000839 emulsion Substances 0.000 description 9
• 150000002632 lipids Chemical class 0.000 description 9
• 229940002612 prodrug Drugs 0.000 description 9
• 239000000651 prodrug Substances 0.000 description 9
• 239000000243 solution Substances 0.000 description 9
• KDCGOANMDULRCW-UHFFFAOYSA-N Purine Natural products N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 8
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 8
• UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• 230000001225 therapeutic effect Effects 0.000 description 8
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 7
• 108091027305 Heteroduplex Proteins 0.000 description 7
• 235000014113 dietary fatty acids Nutrition 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 229930195729 fatty acid Natural products 0.000 description 7
• 239000000194 fatty acid Substances 0.000 description 7
• 239000000499 gel Substances 0.000 description 7
• 238000009396 hybridization Methods 0.000 description 7
• 239000000463 material Substances 0.000 description 7
• 239000004094 surface-active agent Substances 0.000 description 7
• 108700028369 Alleles Proteins 0.000 description 6
• QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
• 108700024394 Exon Proteins 0.000 description 6
• GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 6
• UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 6
• 206010028372 Muscular weakness Diseases 0.000 description 6
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
• PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 6
• HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 6
• 150000001412 amines Chemical class 0.000 description 6
• 230000000903 blocking effect Effects 0.000 description 6
• 230000008499 blood brain barrier function Effects 0.000 description 6
• 210000001218 blood-brain barrier Anatomy 0.000 description 6
• 210000003169 central nervous system Anatomy 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 150000004665 fatty acids Chemical class 0.000 description 6
• 229960002949 fluorouracil Drugs 0.000 description 6
• 230000014759 maintenance of location Effects 0.000 description 6
• 210000000653 nervous system Anatomy 0.000 description 6
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
• 230000009467 reduction Effects 0.000 description 6
• 230000002829 reductive effect Effects 0.000 description 6
• 230000003584 silencer Effects 0.000 description 6
• 210000002027 skeletal muscle Anatomy 0.000 description 6
• 238000006467 substitution reaction Methods 0.000 description 6
• 239000003981 vehicle Substances 0.000 description 6
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 5
• 229930024421 Adenine Natural products 0.000 description 5
• GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 5
• 108020000948 Antisense Oligonucleotides Proteins 0.000 description 5
• HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 5
• 208000010428 Muscle Weakness Diseases 0.000 description 5
• 108091028043 Nucleic acid sequence Proteins 0.000 description 5
• 229960000643 adenine Drugs 0.000 description 5
• 125000003277 amino group Chemical group 0.000 description 5
• 239000002246 antineoplastic agent Substances 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 238000003776 cleavage reaction Methods 0.000 description 5
• 125000004122 cyclic group Chemical group 0.000 description 5
• 210000002216 heart Anatomy 0.000 description 5
• 239000001257 hydrogen Substances 0.000 description 5
• 238000010255 intramuscular injection Methods 0.000 description 5
• 239000007927 intramuscular injection Substances 0.000 description 5
• 210000004185 liver Anatomy 0.000 description 5
• 230000001404 mediated effect Effects 0.000 description 5
• 238000003199 nucleic acid amplification method Methods 0.000 description 5
• 230000007017 scission Effects 0.000 description 5
• 125000001424 substituent group Chemical group 0.000 description 5
• 229940124597 therapeutic agent Drugs 0.000 description 5
• 230000032258 transport Effects 0.000 description 5
• 101100236307 Homo sapiens GAA gene Proteins 0.000 description 4
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 4
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 4
• 208000004756 Respiratory Insufficiency Diseases 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
• 230000003321 amplification Effects 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 239000008280 blood Substances 0.000 description 4
• 230000015556 catabolic process Effects 0.000 description 4
• 238000012512 characterization method Methods 0.000 description 4
• 239000002299 complementary DNA Substances 0.000 description 4
• 239000000562 conjugate Substances 0.000 description 4
• 229940104302 cytosine Drugs 0.000 description 4
• 229940127089 cytotoxic agent Drugs 0.000 description 4
• 238000006731 degradation reaction Methods 0.000 description 4
• 208000035475 disorder Diseases 0.000 description 4
• 230000001747 exhibiting effect Effects 0.000 description 4
• 125000000524 functional group Chemical group 0.000 description 4
• 238000000338 in vitro Methods 0.000 description 4
• 238000005259 measurement Methods 0.000 description 4
• 229960000485 methotrexate Drugs 0.000 description 4
• 239000002777 nucleoside Substances 0.000 description 4
• 230000035699 permeability Effects 0.000 description 4
• DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical group CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 4
• 150000004713 phosphodiesters Chemical class 0.000 description 4
• 230000006461 physiological response Effects 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 102000004196 processed proteins & peptides Human genes 0.000 description 4
• 150000003230 pyrimidines Chemical class 0.000 description 4
• 238000011160 research Methods 0.000 description 4
• 201000004193 respiratory failure Diseases 0.000 description 4
• 239000007787 solid Substances 0.000 description 4
• 239000000725 suspension Substances 0.000 description 4
• 238000012360 testing method Methods 0.000 description 4
• 230000000699 topical effect Effects 0.000 description 4
• MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
• 108060002716 Exonuclease Proteins 0.000 description 3
• 239000004471 Glycine Substances 0.000 description 3
• 108091092195 Intron Proteins 0.000 description 3
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 230000009471 action Effects 0.000 description 3
• 239000004480 active ingredient Substances 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 125000003545 alkoxy group Chemical group 0.000 description 3
• WQZGKKKJIJFFOK-DVKNGEFBSA-N alpha-D-glucose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-DVKNGEFBSA-N 0.000 description 3
• 125000000539 amino acid group Chemical group 0.000 description 3
• 239000003242 anti bacterial agent Substances 0.000 description 3
• 210000004369 blood Anatomy 0.000 description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 125000004432 carbon atom Chemical group C* 0.000 description 3
• 125000002843 carboxylic acid group Chemical group 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 230000001413 cellular effect Effects 0.000 description 3
• 230000036755 cellular response Effects 0.000 description 3
• 230000004700 cellular uptake Effects 0.000 description 3
• 239000002738 chelating agent Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 238000002716 delivery method Methods 0.000 description 3
• 238000013461 design Methods 0.000 description 3
• 238000001514 detection method Methods 0.000 description 3
• 239000006185 dispersion Substances 0.000 description 3
• 238000004520 electroporation Methods 0.000 description 3
• 238000005516 engineering process Methods 0.000 description 3
• 102000013165 exonuclease Human genes 0.000 description 3
• 230000006870 function Effects 0.000 description 3
• 229930182470 glycoside Natural products 0.000 description 3
• 150000002338 glycosides Chemical class 0.000 description 3
• 238000011534 incubation Methods 0.000 description 3
• 230000003834 intracellular effect Effects 0.000 description 3
• 238000000185 intracerebroventricular administration Methods 0.000 description 3
• 238000001990 intravenous administration Methods 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 239000007937 lozenge Substances 0.000 description 3
• 210000004698 lymphocyte Anatomy 0.000 description 3
• 230000007246 mechanism Effects 0.000 description 3
• 239000011859 microparticle Substances 0.000 description 3
• 239000002105 nanoparticle Substances 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 3
• 125000005499 phosphonyl group Chemical group 0.000 description 3
• 239000011574 phosphorus Substances 0.000 description 3
• 238000003752 polymerase chain reaction Methods 0.000 description 3
• 229920001184 polypeptide Polymers 0.000 description 3
• 238000012545 processing Methods 0.000 description 3
• 239000011347 resin Substances 0.000 description 3
• 229920005989 resin Polymers 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 239000007790 solid phase Substances 0.000 description 3
• 230000000392 somatic effect Effects 0.000 description 3
• 230000009885 systemic effect Effects 0.000 description 3
• 238000001890 transfection Methods 0.000 description 3
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
• QVVDVENEPNODSI-BTNSXGMBSA-N (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]amino]-5-(diaminomethylidene 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)=O QVVDVENEPNODSI-BTNSXGMBSA-N 0.000 description 2
• BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 2
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 2
• IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 2
• 102000040650 (ribonucleotides)n+m Human genes 0.000 description 2
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 2
• ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical group OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 2
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
• HSHNITRMYYLLCV-UHFFFAOYSA-N 4-methylumbelliferone Chemical compound C1=C(O)C=CC2=C1OC(=O)C=C2C HSHNITRMYYLLCV-UHFFFAOYSA-N 0.000 description 2
• LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 2
• STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 2
• 108091093088 Amplicon Proteins 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 239000004380 Cholic acid Substances 0.000 description 2
• 108091026890 Coding region Proteins 0.000 description 2
• 108020004705 Codon Proteins 0.000 description 2
• 108020004394 Complementary RNA Proteins 0.000 description 2
• UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
• NBSCHQHZLSJFNQ-QTVWNMPRSA-N D-Mannose-6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@@H]1O NBSCHQHZLSJFNQ-QTVWNMPRSA-N 0.000 description 2
• 108010092160 Dactinomycin Proteins 0.000 description 2
• AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
• 108010042407 Endonucleases Proteins 0.000 description 2
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 206010021118 Hypotonia Diseases 0.000 description 2
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 2
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
• 208000007379 Muscle Hypotonia Diseases 0.000 description 2
• NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
• 238000000636 Northern blotting Methods 0.000 description 2
• 241000283973 Oryctolagus cuniculus Species 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 108091005804 Peptidases Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 108020005067 RNA Splice Sites Proteins 0.000 description 2
• 238000012300 Sequence Analysis Methods 0.000 description 2
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 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
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
• AJYQMCHCOGIXMR-IDTAVKCVSA-N [(2r,3s,4r,5r)-5-[6-(4-bromo-2,3-dioxobutyl)sulfanylpurin-9-yl]-3,4-dihydroxyoxolan-2-yl]methyl phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(O)=O)O[C@H]1N1C2=NC=NC(SCC(=O)C(=O)CBr)=C2N=C1 AJYQMCHCOGIXMR-IDTAVKCVSA-N 0.000 description 2
• 230000002159 abnormal effect Effects 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 2
• 229940088710 antibiotic agent Drugs 0.000 description 2
• 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 description 2
• 230000009286 beneficial effect Effects 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-O benzylaminium Chemical compound [NH3+]CC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-O 0.000 description 2
• 239000003833 bile salt Substances 0.000 description 2
• 210000004204 blood vessel Anatomy 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 210000000170 cell membrane Anatomy 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 2
• 235000019416 cholic acid Nutrition 0.000 description 2
• 229960002471 cholic acid Drugs 0.000 description 2
• 239000003184 complementary RNA Substances 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 238000012258 culturing Methods 0.000 description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
• RGWHQCVHVJXOKC-SHYZEUOFSA-J dCTP(4-) Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)C1 RGWHQCVHVJXOKC-SHYZEUOFSA-J 0.000 description 2
• 229960000640 dactinomycin Drugs 0.000 description 2
• STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
• 229960000975 daunorubicin Drugs 0.000 description 2
• GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
• 238000012217 deletion Methods 0.000 description 2
• 230000037430 deletion Effects 0.000 description 2
• KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
• 238000009792 diffusion process Methods 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
• AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 2
• POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 230000009977 dual effect Effects 0.000 description 2
• 230000002121 endocytic effect Effects 0.000 description 2
• 230000002255 enzymatic effect Effects 0.000 description 2
• 238000011156 evaluation Methods 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• ODKNJVUHOIMIIZ-RRKCRQDMSA-N floxuridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ODKNJVUHOIMIIZ-RRKCRQDMSA-N 0.000 description 2
• 229960000961 floxuridine Drugs 0.000 description 2
• 239000012530 fluid Substances 0.000 description 2
• 230000037406 food intake Effects 0.000 description 2
• 229940093915 gynecological organic acid Drugs 0.000 description 2
• IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
• 238000003018 immunoassay Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 238000007912 intraperitoneal administration Methods 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 230000002132 lysosomal effect Effects 0.000 description 2
• 210000004962 mammalian cell Anatomy 0.000 description 2
• 230000000873 masking effect Effects 0.000 description 2
• GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 238000000520 microinjection Methods 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 239000000178 monomer Substances 0.000 description 2
• 210000003205 muscle Anatomy 0.000 description 2
• 229940103023 myozyme Drugs 0.000 description 2
• 238000007899 nucleic acid hybridization Methods 0.000 description 2
• 150000003833 nucleoside derivatives Chemical class 0.000 description 2
• 125000003835 nucleoside group Chemical group 0.000 description 2
• 238000006384 oligomerization reaction Methods 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 230000007170 pathology Effects 0.000 description 2
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
• 230000002974 pharmacogenomic effect Effects 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
• 239000002953 phosphate buffered saline Substances 0.000 description 2
• WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 2
• XYFCBTPGUUZFHI-UHFFFAOYSA-N phosphine group Chemical group P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 125000003367 polycyclic group Chemical group 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 230000002265 prevention Effects 0.000 description 2
• 230000000750 progressive effect Effects 0.000 description 2
• IGFXRKMLLMBKSA-UHFFFAOYSA-N purine Chemical compound N1=C[N]C2=NC=NC2=C1 IGFXRKMLLMBKSA-UHFFFAOYSA-N 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 238000012552 review Methods 0.000 description 2
• 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 2
• 102220063214 rs201185475 Human genes 0.000 description 2
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 239000000829 suppository Substances 0.000 description 2
• LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical compound CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 2
• 238000010998 test method Methods 0.000 description 2
• 239000002562 thickening agent Substances 0.000 description 2
• 125000003396 thiol group Chemical group [H]S* 0.000 description 2
• WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 239000012049 topical pharmaceutical composition Substances 0.000 description 2
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
• 238000001262 western blot Methods 0.000 description 2
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• MRPKNNSABYPGBF-LSCFUAHRSA-N (2r,3r,4s,5r)-2-[6-(benzylamino)purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(NCC=3C=CC=CC=3)=C2N=C1 MRPKNNSABYPGBF-LSCFUAHRSA-N 0.000 description 1
• RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
• FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
• WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
• KSQPABRRLYOJAM-UHFFFAOYSA-N 1-cyclohexyl-3-methyl-1-nitrosourea Chemical compound CNC(=O)N(N=O)C1CCCCC1 KSQPABRRLYOJAM-UHFFFAOYSA-N 0.000 description 1
• HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 description 1
• VSNHCAURESNICA-NJFSPNSNSA-N 1-oxidanylurea Chemical compound N[14C](=O)NO VSNHCAURESNICA-NJFSPNSNSA-N 0.000 description 1
• DBPWSSGDRRHUNT-CEGNMAFCSA-N 17α-hydroxyprogesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 DBPWSSGDRRHUNT-CEGNMAFCSA-N 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 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 1
• HVVJCLFLKMGEIY-UHFFFAOYSA-N 2,3-dioctadecoxypropyl 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCCCCOCC(COP([O-])(=O)OCC[N+](C)(C)C)OCCCCCCCCCCCCCCCCCC HVVJCLFLKMGEIY-UHFFFAOYSA-N 0.000 description 1
• PIINGYXNCHTJTF-UHFFFAOYSA-N 2-(2-azaniumylethylamino)acetate Chemical group NCCNCC(O)=O PIINGYXNCHTJTF-UHFFFAOYSA-N 0.000 description 1
• PBUUPFTVAPUWDE-UGZDLDLSSA-N 2-[[(2S,4S)-2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2lambda5-oxazaphosphinan-4-yl]sulfanyl]ethanesulfonic acid Chemical compound OS(=O)(=O)CCS[C@H]1CCO[P@](=O)(N(CCCl)CCCl)N1 PBUUPFTVAPUWDE-UGZDLDLSSA-N 0.000 description 1
• HPZXCYOKHIEMGN-OXQGGJHDSA-N 2-amino-9-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)-2-(2-phenylacetyl)oxolan-2-yl]-3h-purin-6-one Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@]1(C(=O)CC=2C=CC=CC=2)O[C@H](CO)[C@@H](O)[C@H]1O HPZXCYOKHIEMGN-OXQGGJHDSA-N 0.000 description 1
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
• XIFVTSIIYVGRHJ-UHFFFAOYSA-N 2-n,2-n,4-n,4-n,6-n-pentamethyl-1,3,5-triazine-2,4,6-triamine Chemical compound CNC1=NC(N(C)C)=NC(N(C)C)=N1 XIFVTSIIYVGRHJ-UHFFFAOYSA-N 0.000 description 1
• 101150090724 3 gene Proteins 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
• AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
• SSRFBERYIRRDJN-MWKWWEEBSA-N 4-amino-1-[(2s,3r,4s,5r)-2-benzoyl-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one Chemical compound O=C1N=C(N)C=CN1[C@@]1(C(=O)C=2C=CC=CC=2)[C@H](O)[C@H](O)[C@@H](CO)O1 SSRFBERYIRRDJN-MWKWWEEBSA-N 0.000 description 1
• PSGQCCSGKGJLRL-UHFFFAOYSA-N 4-methyl-2h-chromen-2-one Chemical group C1=CC=CC2=C1OC(=O)C=C2C PSGQCCSGKGJLRL-UHFFFAOYSA-N 0.000 description 1
• TXLINXBIWJYFNR-UHFFFAOYSA-N 4-phenylpyridine-2-carbonitrile Chemical compound C1=NC(C#N)=CC(C=2C=CC=CC=2)=C1 TXLINXBIWJYFNR-UHFFFAOYSA-N 0.000 description 1
• NMUSYJAQQFHJEW-UHFFFAOYSA-N 5-Azacytidine Natural products O=C1N=C(N)N=CN1C1C(O)C(O)C(CO)O1 NMUSYJAQQFHJEW-UHFFFAOYSA-N 0.000 description 1
• NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
• MFEFTTYGMZOIKO-UHFFFAOYSA-N 5-azacytosine Chemical compound NC1=NC=NC(=O)N1 MFEFTTYGMZOIKO-UHFFFAOYSA-N 0.000 description 1
• LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
• KSNXJLQDQOIRIP-UHFFFAOYSA-N 5-iodouracil Chemical compound IC1=CNC(=O)NC1=O KSNXJLQDQOIRIP-UHFFFAOYSA-N 0.000 description 1
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 101710150620 Anionic peptide Proteins 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• 108010006654 Bleomycin Proteins 0.000 description 1
• 206010006100 Bradykinesia Diseases 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 101100505161 Caenorhabditis elegans mel-32 gene Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 208000031229 Cardiomyopathies Diseases 0.000 description 1
• DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
• 208000011359 Chromosome disease Diseases 0.000 description 1
• WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
• 108020004635 Complementary DNA Proteins 0.000 description 1
• 206010011224 Cough Diseases 0.000 description 1
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 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 1
• 102000053602 DNA Human genes 0.000 description 1
• 229920002307 Dextran Polymers 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 description 1
• 238000002965 ELISA Methods 0.000 description 1
• 102100031780 Endonuclease Human genes 0.000 description 1
• 102000004533 Endonucleases Human genes 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 102000004366 Glucosidases Human genes 0.000 description 1
• 108010056771 Glucosidases Proteins 0.000 description 1
• 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
• 229930186217 Glycolipid Natural products 0.000 description 1
• NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical class C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 208000006083 Hypokinesia Diseases 0.000 description 1
• XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
• XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 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
• 229930010555 Inosine Natural products 0.000 description 1
• UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
• 102100034343 Integrase Human genes 0.000 description 1
• 101710203526 Integrase Proteins 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
• 239000005639 Lauric acid Substances 0.000 description 1
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 206010024971 Lower respiratory tract infections Diseases 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 description 1
• DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 1
• 208000007101 Muscle Cramp Diseases 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 101710149004 Nuclease P1 Proteins 0.000 description 1
• 101710149086 Nuclease S1 Proteins 0.000 description 1
• 108091005461 Nucleic proteins Proteins 0.000 description 1
• 206010061876 Obstruction Diseases 0.000 description 1
• 238000012408 PCR amplification Methods 0.000 description 1
• 229930012538 Paclitaxel Natural products 0.000 description 1
• 235000021314 Palmitic acid Nutrition 0.000 description 1
• 229920002873 Polyethylenimine Polymers 0.000 description 1
• 108010039918 Polylysine Proteins 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 238000002123 RNA extraction Methods 0.000 description 1
• 206010038687 Respiratory distress Diseases 0.000 description 1
• 102000006382 Ribonucleases Human genes 0.000 description 1
• 108010083644 Ribonucleases Proteins 0.000 description 1
• 241001635911 Sarepta Species 0.000 description 1
• 101100311330 Schizosaccharomyces pombe (strain 972 / ATCC 24843) uap56 gene Proteins 0.000 description 1
• 108020004682 Single-Stranded DNA Proteins 0.000 description 1
• 108091081024 Start codon Proteins 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• GFKPPJZEOXIRFX-UHFFFAOYSA-N TCA A Natural products CC(CCC(=O)O)C1=CCC2(C)OC3=C(CC12)C(=O)C(O)CC3 GFKPPJZEOXIRFX-UHFFFAOYSA-N 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
• 101100388071 Thermococcus sp. (strain GE8) pol gene Proteins 0.000 description 1
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
• OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 description 1
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 239000003070 absorption delaying agent Substances 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Chemical group CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
• 239000008351 acetate buffer Substances 0.000 description 1
• 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 1
• 229960004150 aciclovir Drugs 0.000 description 1
• 239000003377 acid catalyst Substances 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 238000012382 advanced drug delivery Methods 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 230000001476 alcoholic effect Effects 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 125000005036 alkoxyphenyl group Chemical group 0.000 description 1
• 229960000473 altretamine Drugs 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 125000006242 amine protecting group Chemical group 0.000 description 1
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
• 229960001220 amsacrine Drugs 0.000 description 1
• 238000010171 animal model Methods 0.000 description 1
• 238000000137 annealing Methods 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 229940124599 anti-inflammatory drug Drugs 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 229940037157 anticorticosteroids Drugs 0.000 description 1
• 229940121375 antifungal agent Drugs 0.000 description 1
• 239000003429 antifungal agent Substances 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
• 125000005160 aryl oxy alkyl group Chemical group 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 235000003704 aspartic acid Nutrition 0.000 description 1
• 238000003149 assay kit Methods 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 229960002756 azacitidine Drugs 0.000 description 1
• 229910052788 barium Inorganic materials 0.000 description 1
• DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
• 230000006399 behavior Effects 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
• 239000003613 bile acid Substances 0.000 description 1
• 229940093761 bile salts Drugs 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 238000010876 biochemical test Methods 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 239000012472 biological sample Substances 0.000 description 1
• 229960001561 bleomycin Drugs 0.000 description 1
• OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
• 210000001124 body fluid Anatomy 0.000 description 1
• 239000010839 body fluid Substances 0.000 description 1
• 230000036760 body temperature Effects 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 238000010322 bone marrow transplantation Methods 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 229960002092 busulfan Drugs 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
• 210000001217 buttock Anatomy 0.000 description 1
• 238000010804 cDNA synthesis Methods 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229960005069 calcium Drugs 0.000 description 1
• 239000001506 calcium phosphate Substances 0.000 description 1
• 229960001714 calcium phosphate Drugs 0.000 description 1
• 229910000389 calcium phosphate Inorganic materials 0.000 description 1
• 235000011010 calcium phosphates Nutrition 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 125000000837 carbohydrate group Chemical group 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 238000006555 catalytic reaction Methods 0.000 description 1
• 150000001767 cationic compounds Chemical class 0.000 description 1
• 239000013592 cell lysate Substances 0.000 description 1
• 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
• 125000003636 chemical group Chemical group 0.000 description 1
• 229940044683 chemotherapy drug Drugs 0.000 description 1
• 230000001055 chewing effect Effects 0.000 description 1
• JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
• 229960004630 chlorambucil Drugs 0.000 description 1
• 208000024971 chromosomal disease Diseases 0.000 description 1
• 230000002759 chromosomal effect Effects 0.000 description 1
• 235000013985 cinnamic acid Nutrition 0.000 description 1
• 229930016911 cinnamic acid Natural products 0.000 description 1
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
• 229960004316 cisplatin Drugs 0.000 description 1
• 238000011260 co-administration Methods 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 229960001338 colchicine Drugs 0.000 description 1
• 238000004891 communication Methods 0.000 description 1
• 239000008139 complexing agent Substances 0.000 description 1
• 229940125898 compound 5 Drugs 0.000 description 1
• 239000002872 contrast media Substances 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 229960004397 cyclophosphamide Drugs 0.000 description 1
• 208000031513 cyst Diseases 0.000 description 1
• 229960000684 cytarabine Drugs 0.000 description 1
• 210000000805 cytoplasm Anatomy 0.000 description 1
• 229960003901 dacarbazine Drugs 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• 230000007812 deficiency Effects 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 239000007857 degradation product Substances 0.000 description 1
• 230000003111 delayed effect Effects 0.000 description 1
• 229940124447 delivery agent Drugs 0.000 description 1
• 210000000852 deltoid muscle Anatomy 0.000 description 1
• CFCUWKMKBJTWLW-UHFFFAOYSA-N deoliosyl-3C-alpha-L-digitoxosyl-MTM Natural products CC=1C(O)=C2C(O)=C3C(=O)C(OC4OC(C)C(O)C(OC5OC(C)C(O)C(OC6OC(C)C(O)C(C)(O)C6)C5)C4)C(C(OC)C(=O)C(O)C(C)O)CC3=CC2=CC=1OC(OC(C)C1O)CC1OC1CC(O)C(O)C(C)O1 CFCUWKMKBJTWLW-UHFFFAOYSA-N 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• 230000001687 destabilization Effects 0.000 description 1
• 230000000368 destabilizing effect Effects 0.000 description 1
• 238000006642 detritylation reaction Methods 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000000378 dietary effect Effects 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 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 1
• 230000008034 disappearance Effects 0.000 description 1
• 231100000673 dose–response relationship Toxicity 0.000 description 1
• 229960004679 doxorubicin Drugs 0.000 description 1
• 239000006196 drop Substances 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 239000003596 drug target Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 229960001904 epirubicin Drugs 0.000 description 1
• 230000008029 eradication Effects 0.000 description 1
• ITSGNOIFAJAQHJ-BMFNZSJVSA-N esorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)C[C@H](C)O1 ITSGNOIFAJAQHJ-BMFNZSJVSA-N 0.000 description 1
• 229950002017 esorubicin Drugs 0.000 description 1
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 239000000796 flavoring agent Substances 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
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 230000037433 frameshift Effects 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 229960002963 ganciclovir Drugs 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
• 229960005277 gemcitabine Drugs 0.000 description 1
• 238000012224 gene deletion Methods 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 125000005059 halophenyl group Chemical group 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 239000000017 hydrogel Substances 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• 238000007327 hydrogenolysis reaction Methods 0.000 description 1
• 229920001477 hydrophilic polymer Polymers 0.000 description 1
• 125000001165 hydrophobic group Chemical group 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
• 229960002899 hydroxyprogesterone Drugs 0.000 description 1
• 229960000908 idarubicin Drugs 0.000 description 1
• HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
• 229960001101 ifosfamide Drugs 0.000 description 1
• 230000001900 immune effect Effects 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 230000006872 improvement Effects 0.000 description 1
• 238000000126 in silico method Methods 0.000 description 1
• 239000005414 inactive ingredient Substances 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229910001411 inorganic cation Inorganic materials 0.000 description 1
• 229960003786 inosine Drugs 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 238000001361 intraarterial administration Methods 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 239000007928 intraperitoneal injection Substances 0.000 description 1
• NTHXOOBQLCIOLC-UHFFFAOYSA-N iohexol Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NTHXOOBQLCIOLC-UHFFFAOYSA-N 0.000 description 1
• 229960001025 iohexol Drugs 0.000 description 1
• UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
• 229960004768 irinotecan Drugs 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 210000000265 leukocyte Anatomy 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 239000008206 lipophilic material Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 238000007449 liver function test Methods 0.000 description 1
• 230000004807 localization Effects 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 210000004324 lymphatic system Anatomy 0.000 description 1
• 210000003712 lysosome Anatomy 0.000 description 1
• 230000001868 lysosomic effect Effects 0.000 description 1
• 229920002521 macromolecule Polymers 0.000 description 1
• 229950000547 mafosfamide Drugs 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 238000012423 maintenance Methods 0.000 description 1
• 238000011418 maintenance treatment Methods 0.000 description 1
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000010534 mechanism of action Effects 0.000 description 1
• HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical class ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 1
• 229960004961 mechlorethamine Drugs 0.000 description 1
• SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 1
• 229960001924 melphalan Drugs 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 210000004379 membrane Anatomy 0.000 description 1
• 229960001428 mercaptopurine Drugs 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
• 239000004530 micro-emulsion Substances 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 239000004005 microsphere Substances 0.000 description 1
• CFCUWKMKBJTWLW-BKHRDMLASA-N mithramycin Chemical compound O([C@@H]1C[C@@H](O[C@H](C)[C@H]1O)OC=1C=C2C=C3C[C@H]([C@@H](C(=O)C3=C(O)C2=C(O)C=1C)O[C@@H]1O[C@H](C)[C@@H](O)[C@H](O[C@@H]2O[C@H](C)[C@H](O)[C@H](O[C@@H]3O[C@H](C)[C@@H](O)[C@@](C)(O)C3)C2)C1)[C@H](OC)C(=O)[C@@H](O)[C@@H](C)O)[C@H]1C[C@@H](O)[C@H](O)[C@@H](C)O1 CFCUWKMKBJTWLW-BKHRDMLASA-N 0.000 description 1
• 229960004857 mitomycin Drugs 0.000 description 1
• KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
• 229960001156 mitoxantrone Drugs 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 210000004400 mucous membrane Anatomy 0.000 description 1
• 238000001964 muscle biopsy Methods 0.000 description 1
• WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 229930014626 natural product Natural products 0.000 description 1
• 239000006199 nebulizer Substances 0.000 description 1
• 230000001537 neural effect Effects 0.000 description 1
• 210000002569 neuron Anatomy 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 125000006574 non-aromatic ring group Chemical group 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 238000003499 nucleic acid array Methods 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 150000002892 organic cations Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 230000008520 organization Effects 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 229910052760 oxygen Inorganic materials 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 229960001592 paclitaxel Drugs 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000001575 pathological effect Effects 0.000 description 1
• 229960002340 pentostatin Drugs 0.000 description 1
• FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 description 1
• 239000000863 peptide conjugate Substances 0.000 description 1
• 210000005259 peripheral blood Anatomy 0.000 description 1
• 239000011886 peripheral blood Substances 0.000 description 1
• 210000002856 peripheral neuron Anatomy 0.000 description 1
• 230000008823 permeabilization Effects 0.000 description 1
• 239000008251 pharmaceutical emulsion Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229940127557 pharmaceutical product Drugs 0.000 description 1
• 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001095 phosphatidyl group Chemical group 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 230000037081 physical activity Effects 0.000 description 1
• 230000004962 physiological condition Effects 0.000 description 1
• BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 description 1
• 229960003171 plicamycin Drugs 0.000 description 1
• 229920000656 polylysine Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
• 229960004618 prednisone Drugs 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 150000003141 primary amines Chemical group 0.000 description 1
• CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
• 229960000624 procarbazine Drugs 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 238000004393 prognosis Methods 0.000 description 1
• 230000000644 propagated effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 230000004952 protein activity Effects 0.000 description 1
• 230000004853 protein function Effects 0.000 description 1
• 238000001742 protein purification Methods 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 150000003212 purines Chemical class 0.000 description 1
• 210000003314 quadriceps muscle Anatomy 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 238000003753 real-time PCR Methods 0.000 description 1
• 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
• 230000000306 recurrent effect Effects 0.000 description 1
• 230000014891 regulation of alternative nuclear mRNA splicing, via spliceosome Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000009877 rendering Methods 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 230000004043 responsiveness Effects 0.000 description 1
• 238000012340 reverse transcriptase PCR Methods 0.000 description 1
• 239000002342 ribonucleoside Substances 0.000 description 1
• 150000003290 ribose derivatives Chemical class 0.000 description 1
• 125000006413 ring segment Chemical group 0.000 description 1
• 102200163772 rs28940868 Human genes 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 239000000523 sample Substances 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 231100000004 severe toxicity Toxicity 0.000 description 1
• 238000007493 shaping process Methods 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• 108010062513 snake venom phosphodiesterase I Proteins 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000011780 sodium chloride Substances 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• JJICLMJFIKGAAU-UHFFFAOYSA-M sodium;2-amino-9-(1,3-dihydroxypropan-2-yloxymethyl)purin-6-olate Chemical compound [Na+].NC1=NC([O-])=C2N=CN(COC(CO)CO)C2=N1 JJICLMJFIKGAAU-UHFFFAOYSA-M 0.000 description 1
• RMLUKZWYIKEASN-UHFFFAOYSA-M sodium;2-amino-9-(2-hydroxyethoxymethyl)purin-6-olate Chemical compound [Na+].O=C1[N-]C(N)=NC2=C1N=CN2COCCO RMLUKZWYIKEASN-UHFFFAOYSA-M 0.000 description 1
• 238000010532 solid phase synthesis reaction Methods 0.000 description 1
• 239000002904 solvent Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 108010068698 spleen exonuclease Proteins 0.000 description 1
• 230000037423 splicing regulation Effects 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 230000006641 stabilisation Effects 0.000 description 1
• 238000011105 stabilization Methods 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• 108010075210 streptolysin O Proteins 0.000 description 1
• 101150018444 sub2 gene Proteins 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• 150000008163 sugars Chemical group 0.000 description 1
• 230000019635 sulfation Effects 0.000 description 1
• 238000005670 sulfation reaction Methods 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 239000011593 sulfur Substances 0.000 description 1
• 230000009469 supplementation Effects 0.000 description 1
• 230000004083 survival effect Effects 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 230000009747 swallowing Effects 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• 229960001603 tamoxifen Drugs 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
• NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 1
• 229960001278 teniposide Drugs 0.000 description 1
• 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 229960003604 testosterone Drugs 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 238000011285 therapeutic regimen Methods 0.000 description 1
• 229960003087 tioguanine Drugs 0.000 description 1
• UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
• 229960000303 topotecan Drugs 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 0.000 description 1
• 238000010361 transduction Methods 0.000 description 1
• 230000026683 transduction Effects 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 230000005945 translocation Effects 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
• NOYPYLRCIDNJJB-UHFFFAOYSA-O trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=[NH+]C(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-O 0.000 description 1
• 229960001099 trimetrexate Drugs 0.000 description 1
• JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
• 210000000689 upper leg Anatomy 0.000 description 1
• 238000011144 upstream manufacturing Methods 0.000 description 1
• 210000002700 urine Anatomy 0.000 description 1
• RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
• 239000004474 valine Substances 0.000 description 1
• 230000002861 ventricular Effects 0.000 description 1
• 229960003636 vidarabine Drugs 0.000 description 1
• 229960003048 vinblastine Drugs 0.000 description 1
• JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
• OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
• 229960004528 vincristine Drugs 0.000 description 1
• OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
• 239000013603 viral vector Substances 0.000 description 1
• 230000003612 virological effect Effects 0.000 description 1
• 238000012800 visualization Methods 0.000 description 1
• 230000003442 weekly effect Effects 0.000 description 1
• 230000004580 weight loss Effects 0.000 description 1