JP2017535552A5 - - Google Patents

Info

Publication number

JP2017535552A5

JP2017535552A5 JP2017526493A JP2017526493A JP2017535552A5 JP 2017535552 A5 JP2017535552 A5 JP 2017535552A5 JP 2017526493 A JP2017526493 A JP 2017526493A JP 2017526493 A JP2017526493 A JP 2017526493A JP 2017535552 A5 JP2017535552 A5 JP 2017535552A5

Authority

JP

Japan

Prior art keywords

double

nucleotides

rnai agent

nucleotide

stranded rnai

Prior art date

2015-11-17

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Pending

Links

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• 125000003729 nucleotide group Chemical group 0.000 claims 90
• 239000002773 nucleotide Substances 0.000 claims 75
• 239000003795 chemical substances by application Substances 0.000 claims 63
• 108091030071 RNAI Proteins 0.000 claims 62
• 230000009368 gene silencing by RNA Effects 0.000 claims 62
• 108091081021 Sense strand Proteins 0.000 claims 26
• 230000000692 anti-sense effect Effects 0.000 claims 25
• 108010056301 Apolipoprotein C-III Proteins 0.000 claims 16
• 102100030970 Apolipoprotein C-III Human genes 0.000 claims 16
• 238000012986 modification Methods 0.000 claims 15
• 230000004048 modification Effects 0.000 claims 15
• 239000003446 ligand Substances 0.000 claims 14
• 229910019142 PO4 Inorganic materials 0.000 claims 10
• 239000010452 phosphate Substances 0.000 claims 10
• 239000000203 mixture Substances 0.000 claims 7
• 230000002401 inhibitory effect Effects 0.000 claims 6
• RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims 5
• OVRNDRQMDRJTHS-KEWYIRBNSA-N N-acetyl-D-galactosamine Chemical class CC(=O)N[C@H]1C(O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-KEWYIRBNSA-N 0.000 claims 4
• 230000003278 mimic effect Effects 0.000 claims 4
• 108020004707 nucleic acids Proteins 0.000 claims 4
• 102000039446 nucleic acids Human genes 0.000 claims 4
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 4
• KBDWGFZSICOZSJ-UHFFFAOYSA-N 5-methyl-2,3-dihydro-1H-pyrimidin-4-one Chemical group N1CNC=C(C1=O)C KBDWGFZSICOZSJ-UHFFFAOYSA-N 0.000 claims 2
• 208000035657 Abasia Diseases 0.000 claims 2
• 108091034117 Oligonucleotide Proteins 0.000 claims 2
• HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol group Chemical group [C@@H]1(CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)[C@H](C)CCCC(C)C HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims 2
• 230000000295 complement effect Effects 0.000 claims 2
• 201000010099 disease Diseases 0.000 claims 2
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
• BNKAXGCRDYRABM-UHFFFAOYSA-N ethenyl dihydrogen phosphate Chemical compound OP(O)(=O)OC=C BNKAXGCRDYRABM-UHFFFAOYSA-N 0.000 claims 2
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
• 125000001921 locked nucleotide group Chemical group 0.000 claims 2
• YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 claims 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
• ONKSSDKXDIVIHK-UHFFFAOYSA-N n,n-didecyldodecanamide Chemical group CCCCCCCCCCCC(=O)N(CCCCCCCCCC)CCCCCCCCCC ONKSSDKXDIVIHK-UHFFFAOYSA-N 0.000 claims 2
• 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 2
• 229910052760 oxygen Inorganic materials 0.000 claims 2
• PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims 2
• 229910052717 sulfur Inorganic materials 0.000 claims 2
• -1 thymidine-glycol nucleic acid Chemical class 0.000 claims 2
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 2
• MPCAJMNYNOGXPB-UHFFFAOYSA-N 1,5-Anhydro-mannit Natural products OCC1OCC(O)C(O)C1O MPCAJMNYNOGXPB-UHFFFAOYSA-N 0.000 claims 1
• QQMSZHORHNORLP-KVQBGUIXSA-N 2'-deoxyguanosine 3'-monophosphate Chemical compound C1=NC=2C(=O)NC(N)=NC=2N1[C@H]1C[C@H](OP(O)(O)=O)[C@@H](CO)O1 QQMSZHORHNORLP-KVQBGUIXSA-N 0.000 claims 1
• QQMSZHORHNORLP-UHFFFAOYSA-N 2'-deoxyguanosine 3'-monophosphate Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1CC(OP(O)(O)=O)C(CO)O1 QQMSZHORHNORLP-UHFFFAOYSA-N 0.000 claims 1
• 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 claims 1
• 201000001320 Atherosclerosis Diseases 0.000 claims 1
• 206010020772 Hypertension Diseases 0.000 claims 1
• 206010022489 Insulin Resistance Diseases 0.000 claims 1
• 206010023230 Joint stiffness Diseases 0.000 claims 1
• 208000008589 Obesity Diseases 0.000 claims 1
• 206010033645 Pancreatitis Diseases 0.000 claims 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims 1
• RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical class OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims 1
• 239000002253 acid Substances 0.000 claims 1
• 208000006575 hypertriglyceridemia Diseases 0.000 claims 1
• 208000017169 kidney disease Diseases 0.000 claims 1
• 108020004999 messenger RNA Proteins 0.000 claims 1
• 238000000034 method Methods 0.000 claims 1
• 229910052757 nitrogen Inorganic materials 0.000 claims 1
• 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 1
• 150000007523 nucleic acids Chemical class 0.000 claims 1
• 235000020824 obesity Nutrition 0.000 claims 1
• 239000008194 pharmaceutical composition Substances 0.000 claims 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 claims 1
• 229910052698 phosphorus Inorganic materials 0.000 claims 1
• 239000011574 phosphorus Substances 0.000 claims 1
• 201000010065 polycystic ovary syndrome Diseases 0.000 claims 1
• 0 C*C1C(*)C(OCCCCC(NCCCNC(CCOCC(C)(COCCC(NCCCC(C)*(C)C(CCCCOC(C(*)C2O)OC(CO)C2O)=O)=O)COCCC(NCCCNC(CCCCOC(*C(CO)C2O)C(*)C2O)=O)=O)=O)=O)OC(CO)C1* Chemical compound C*C1C(*)C(OCCCCC(NCCCNC(CCOCC(C)(COCCC(NCCCC(C)*(C)C(CCCCOC(C(*)C2O)OC(CO)C2O)=O)=O)COCCC(NCCCNC(CCCCOC(*C(CO)C2O)C(*)C2O)=O)=O)=O)=O)OC(CO)C1* 0.000 description 1