TW200838551A - Methods for treating hypercholesterolemia - Google Patents
Methods for treating hypercholesterolemia Download PDFInfo
- Publication number
- TW200838551A TW200838551A TW096145015A TW96145015A TW200838551A TW 200838551 A TW200838551 A TW 200838551A TW 096145015 A TW096145015 A TW 096145015A TW 96145015 A TW96145015 A TW 96145015A TW 200838551 A TW200838551 A TW 200838551A
- Authority
- TW
- Taiwan
- Prior art keywords
- seq
- compound
- doc
- modified
- cholesterol
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 241
- 208000035150 Hypercholesterolemia Diseases 0.000 title claims abstract description 42
- 150000001875 compounds Chemical class 0.000 claims abstract description 867
- 230000000692 anti-sense effect Effects 0.000 claims abstract description 759
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 322
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 304
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 304
- 101001098868 Homo sapiens Proprotein convertase subtilisin/kexin type 9 Proteins 0.000 claims abstract description 287
- 102100038955 Proprotein convertase subtilisin/kexin type 9 Human genes 0.000 claims abstract description 274
- 108010028554 LDL Cholesterol Proteins 0.000 claims abstract description 123
- 208000029078 coronary artery disease Diseases 0.000 claims abstract description 108
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 50
- 239000000074 antisense oligonucleotide Substances 0.000 claims abstract description 39
- 238000012230 antisense oligonucleotides Methods 0.000 claims abstract description 39
- 238000011282 treatment Methods 0.000 claims abstract description 31
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims abstract description 10
- 125000003729 nucleotide group Chemical group 0.000 claims description 859
- 239000002773 nucleotide Substances 0.000 claims description 813
- 241000764238 Isis Species 0.000 claims description 190
- ABEXEQSGABRUHS-UHFFFAOYSA-N 16-methylheptadecyl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC(C)C ABEXEQSGABRUHS-UHFFFAOYSA-N 0.000 claims description 178
- 238000005417 image-selected in vivo spectroscopy Methods 0.000 claims description 178
- 238000012739 integrated shape imaging system Methods 0.000 claims description 178
- 239000002777 nucleoside Substances 0.000 claims description 138
- 239000012634 fragment Substances 0.000 claims description 125
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 115
- 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 description 114
- 108091034117 Oligonucleotide Proteins 0.000 claims description 113
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 83
- 230000000295 complement effect Effects 0.000 claims description 82
- 235000000346 sugar Nutrition 0.000 claims description 81
- 238000002560 therapeutic procedure Methods 0.000 claims description 69
- 210000002966 serum Anatomy 0.000 claims description 61
- 235000012000 cholesterol Nutrition 0.000 claims description 54
- 125000003835 nucleoside group Chemical group 0.000 claims description 50
- 239000002253 acid Substances 0.000 claims description 49
- 108010023302 HDL Cholesterol Proteins 0.000 claims description 48
- 230000008685 targeting Effects 0.000 claims description 45
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 43
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 43
- 230000009467 reduction Effects 0.000 claims description 42
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 38
- 239000002245 particle Substances 0.000 claims description 35
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 35
- 239000008194 pharmaceutical composition Substances 0.000 claims description 34
- 238000008214 LDL Cholesterol Methods 0.000 claims description 33
- 150000002632 lipids Chemical group 0.000 claims description 32
- 108010069201 VLDL Cholesterol Proteins 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 29
- 108091028043 Nucleic acid sequence Proteins 0.000 claims description 26
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 24
- 230000000694 effects Effects 0.000 claims description 24
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical group [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 23
- 108010007622 LDL Lipoproteins Proteins 0.000 claims description 22
- 241001465754 Metazoa Species 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 206010019708 Hepatic steatosis Diseases 0.000 claims description 19
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 19
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 18
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 18
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 17
- 108010010234 HDL Lipoproteins Proteins 0.000 claims description 16
- 229940079593 drug Drugs 0.000 claims description 16
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 16
- 230000004048 modification Effects 0.000 claims description 16
- 238000012986 modification Methods 0.000 claims description 16
- 230000006872 improvement Effects 0.000 claims description 15
- 108010062497 VLDL Lipoproteins Proteins 0.000 claims description 14
- 125000002619 bicyclic group Chemical group 0.000 claims description 14
- 238000007911 parenteral administration Methods 0.000 claims description 14
- 230000003234 polygenic effect Effects 0.000 claims description 14
- 230000001225 therapeutic effect Effects 0.000 claims description 14
- 208000013824 Acidemia Diseases 0.000 claims description 13
- 208000010444 Acidosis Diseases 0.000 claims description 13
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 13
- 150000003904 phospholipids Chemical class 0.000 claims description 13
- 206010036790 Productive cough Diseases 0.000 claims description 12
- 208000006575 hypertriglyceridemia Diseases 0.000 claims description 12
- 230000002829 reductive effect Effects 0.000 claims description 12
- 208000024794 sputum Diseases 0.000 claims description 12
- 229940122502 Cholesterol absorption inhibitor Drugs 0.000 claims description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 11
- 239000003112 inhibitor Substances 0.000 claims description 11
- -1 monomethoxyethyl group Chemical group 0.000 claims description 11
- 210000003802 sputum Anatomy 0.000 claims description 11
- 229960000815 ezetimibe Drugs 0.000 claims description 10
- OLNTVTPDXPETLC-XPWALMASSA-N ezetimibe Chemical compound N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 OLNTVTPDXPETLC-XPWALMASSA-N 0.000 claims description 10
- 230000002440 hepatic effect Effects 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 9
- 230000008859 change Effects 0.000 claims description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims description 9
- 230000005764 inhibitory process Effects 0.000 claims description 9
- 238000001990 intravenous administration Methods 0.000 claims description 9
- 229960002855 simvastatin Drugs 0.000 claims description 9
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 9
- 150000003626 triacylglycerols Chemical class 0.000 claims description 9
- 102100040214 Apolipoprotein(a) Human genes 0.000 claims description 8
- 101710115418 Apolipoprotein(a) Proteins 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 239000008187 granular material Substances 0.000 claims description 8
- 238000007920 subcutaneous administration Methods 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 108010027006 Apolipoproteins B Proteins 0.000 claims description 7
- 102000018616 Apolipoproteins B Human genes 0.000 claims description 7
- 206010020772 Hypertension Diseases 0.000 claims description 7
- 210000004369 blood Anatomy 0.000 claims description 7
- 239000008280 blood Substances 0.000 claims description 7
- 239000003085 diluting agent Substances 0.000 claims description 7
- 238000009396 hybridization Methods 0.000 claims description 7
- 206010003210 Arteriosclerosis Diseases 0.000 claims description 6
- 208000037260 Atherosclerotic Plaque Diseases 0.000 claims description 6
- 102100031545 Microsomal triglyceride transfer protein large subunit Human genes 0.000 claims description 6
- 229940123934 Reductase inhibitor Drugs 0.000 claims description 6
- 238000009472 formulation Methods 0.000 claims description 6
- 230000002068 genetic effect Effects 0.000 claims description 6
- 208000019622 heart disease Diseases 0.000 claims description 6
- 229960000672 rosuvastatin Drugs 0.000 claims description 6
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 6
- 230000000391 smoking effect Effects 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 230000002028 premature Effects 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 229930182470 glycoside Natural products 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 108010022197 lipoprotein cholesterol Proteins 0.000 claims description 4
- 208000024891 symptom Diseases 0.000 claims description 4
- CABVTRNMFUVUDM-VRHQGPGLSA-N (3S)-3-hydroxy-3-methylglutaryl-CoA Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCSC(=O)C[C@@](O)(CC(O)=O)C)O[C@H]1N1C2=NC=NC(N)=C2N=C1 CABVTRNMFUVUDM-VRHQGPGLSA-N 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- 208000004930 Fatty Liver Diseases 0.000 claims description 3
- 108090000854 Oxidoreductases Proteins 0.000 claims description 3
- 102000004316 Oxidoreductases Human genes 0.000 claims description 3
- 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 Chemical class Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 3
- 238000003556 assay Methods 0.000 claims description 3
- 150000001720 carbohydrates Chemical class 0.000 claims description 3
- 210000004027 cell Anatomy 0.000 claims description 3
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 3
- 239000000194 fatty acid Substances 0.000 claims description 3
- 229930195729 fatty acid Natural products 0.000 claims description 3
- 150000004665 fatty acids Chemical class 0.000 claims description 3
- 125000005456 glyceride group Chemical group 0.000 claims description 3
- 150000002338 glycosides Chemical class 0.000 claims description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 3
- 239000010931 gold Substances 0.000 claims description 3
- 229910052737 gold Inorganic materials 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 229910052698 phosphorus Inorganic materials 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 239000011574 phosphorus Substances 0.000 claims description 2
- 239000002689 soil Substances 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 102000053786 human PCSK9 Human genes 0.000 claims 14
- 230000001154 acute effect Effects 0.000 claims 12
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims 5
- 235000011187 glycerol Nutrition 0.000 claims 4
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims 3
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims 3
- 229960005370 atorvastatin Drugs 0.000 claims 3
- 150000008163 sugars Chemical class 0.000 claims 3
- 241000282412 Homo Species 0.000 claims 2
- 201000005577 familial hyperlipidemia Diseases 0.000 claims 2
- 208000010706 fatty liver disease Diseases 0.000 claims 2
- 235000021419 vinegar Nutrition 0.000 claims 2
- 239000000052 vinegar Substances 0.000 claims 2
- HWPZZUQOWRWFDB-UHFFFAOYSA-N 1-methylcytosine Chemical compound CN1C=CC(N)=NC1=O HWPZZUQOWRWFDB-UHFFFAOYSA-N 0.000 claims 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims 1
- 206010033557 Palpitations Diseases 0.000 claims 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 claims 1
- 244000046052 Phaseolus vulgaris Species 0.000 claims 1
- 108010029485 Protein Isoforms Proteins 0.000 claims 1
- 102000001708 Protein Isoforms Human genes 0.000 claims 1
- 229930182475 S-glycoside Natural products 0.000 claims 1
- 241001000605 Semia Species 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 claims 1
- CBJPDVRRPSGPAF-UHFFFAOYSA-N [Na].[Na].[Na].OCC(O)CO Chemical compound [Na].[Na].[Na].OCC(O)CO CBJPDVRRPSGPAF-UHFFFAOYSA-N 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 claims 1
- 238000011374 additional therapy Methods 0.000 claims 1
- 210000000941 bile Anatomy 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 230000001906 cholesterol absorption Effects 0.000 claims 1
- 229940126545 compound 53 Drugs 0.000 claims 1
- 125000004122 cyclic group Chemical group 0.000 claims 1
- 230000001086 cytosolic effect Effects 0.000 claims 1
- 230000004064 dysfunction Effects 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 125000004383 glucosinolate group Chemical group 0.000 claims 1
- 210000005260 human cell Anatomy 0.000 claims 1
- 150000001261 hydroxy acids Chemical class 0.000 claims 1
- 230000005906 menstruation Effects 0.000 claims 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 claims 1
- FDBYIYFVSAHJLY-UHFFFAOYSA-N resmetirom Chemical compound N1C(=O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)N2C(NC(=O)C(C#N)=N2)=O)Cl)=N1 FDBYIYFVSAHJLY-UHFFFAOYSA-N 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 150000003569 thioglycosides Chemical class 0.000 claims 1
- 238000012795 verification Methods 0.000 claims 1
- 230000003442 weekly effect Effects 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 abstract description 3
- 229920000642 polymer Polymers 0.000 description 28
- 210000002381 plasma Anatomy 0.000 description 20
- 102000007330 LDL Lipoproteins Human genes 0.000 description 19
- 108010001831 LDL receptors Proteins 0.000 description 19
- 102000000853 LDL receptors Human genes 0.000 description 17
- 239000003524 antilipemic agent Substances 0.000 description 16
- 208000000563 Hyperlipoproteinemia Type II Diseases 0.000 description 13
- 102000004895 Lipoproteins Human genes 0.000 description 12
- 108090001030 Lipoproteins Proteins 0.000 description 12
- 206010045261 Type IIa hyperlipidaemia Diseases 0.000 description 10
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 10
- 201000001386 familial hypercholesterolemia Diseases 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 230000035772 mutation Effects 0.000 description 10
- 210000004940 nucleus Anatomy 0.000 description 10
- 102100024640 Low-density lipoprotein receptor Human genes 0.000 description 9
- 210000004185 liver Anatomy 0.000 description 9
- 108020004999 messenger RNA Proteins 0.000 description 7
- 239000008177 pharmaceutical agent Substances 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 6
- 206010064571 Gene mutation Diseases 0.000 description 5
- 108010033266 Lipoprotein(a) Proteins 0.000 description 5
- 102000057248 Lipoprotein(a) Human genes 0.000 description 5
- 230000002411 adverse Effects 0.000 description 5
- 229940104302 cytosine Drugs 0.000 description 5
- 235000019197 fats Nutrition 0.000 description 5
- 238000006467 substitution reaction Methods 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 description 4
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 description 4
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 description 4
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 4
- 102000015779 HDL Lipoproteins Human genes 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 210000001367 artery Anatomy 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 230000007211 cardiovascular event Effects 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N nicotinic acid Natural products OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
- 238000006116 polymerization reaction Methods 0.000 description 4
- 235000018102 proteins Nutrition 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 230000002441 reversible effect Effects 0.000 description 4
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 108020004414 DNA Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000007385 chemical modification Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 238000012217 deletion Methods 0.000 description 3
- 230000037430 deletion Effects 0.000 description 3
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 238000012544 monitoring process Methods 0.000 description 3
- 229960003512 nicotinic acid Drugs 0.000 description 3
- 235000001968 nicotinic acid Nutrition 0.000 description 3
- 239000011664 nicotinic acid Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- YIMATHOGWXZHFX-WCTZXXKLSA-N (2r,3r,4r,5r)-5-(hydroxymethyl)-3-(2-methoxyethoxy)oxolane-2,4-diol Chemical group COCCO[C@H]1[C@H](O)O[C@H](CO)[C@H]1O YIMATHOGWXZHFX-WCTZXXKLSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 2
- 102100026596 Bcl-2-like protein 1 Human genes 0.000 description 2
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- 102000055006 Calcitonin Human genes 0.000 description 2
- 108060001064 Calcitonin Proteins 0.000 description 2
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 206010022095 Injection Site reaction Diseases 0.000 description 2
- 101710105047 Lipoprotein B Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 101150094724 PCSK9 gene Proteins 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000002723 alicyclic group Chemical group 0.000 description 2
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 229920000080 bile acid sequestrant Polymers 0.000 description 2
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 2
- 229960004015 calcitonin Drugs 0.000 description 2
- 125000003178 carboxy group Chemical class [H]OC(*)=O 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 210000000349 chromosome Anatomy 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 235000018823 dietary intake Nutrition 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 229940011871 estrogen Drugs 0.000 description 2
- 239000000262 estrogen Substances 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 2
- 229910052736 halogen Inorganic materials 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- 125000001072 heteroaryl group Chemical group 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000003908 liver function Effects 0.000 description 2
- 238000007449 liver function test Methods 0.000 description 2
- 230000008774 maternal effect Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000008775 paternal effect Effects 0.000 description 2
- 231100000614 poison Toxicity 0.000 description 2
- 231100000572 poisoning Toxicity 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- 231100000759 toxicological effect Toxicity 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 229940035893 uracil Drugs 0.000 description 2
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 description 1
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 1
- VTAKZNRDSPNOAU-UHFFFAOYSA-M 2-(chloromethyl)oxirane;hydron;prop-2-en-1-amine;n-prop-2-enyldecan-1-amine;trimethyl-[6-(prop-2-enylamino)hexyl]azanium;dichloride Chemical compound Cl.[Cl-].NCC=C.ClCC1CO1.CCCCCCCCCCNCC=C.C[N+](C)(C)CCCCCCNCC=C VTAKZNRDSPNOAU-UHFFFAOYSA-M 0.000 description 1
- ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical group OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 1
- 229930024421 Adenine Natural products 0.000 description 1
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 1
- 101150102415 Apob gene Proteins 0.000 description 1
- 102100040202 Apolipoprotein B-100 Human genes 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 206010003130 Arrhythmia supraventricular Diseases 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 229940122361 Bisphosphonate Drugs 0.000 description 1
- 125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000014882 Carotid artery disease Diseases 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 229920002905 Colesevelam Polymers 0.000 description 1
- 108091035707 Consensus sequence Proteins 0.000 description 1
- 102000004420 Creatine Kinase Human genes 0.000 description 1
- 108010042126 Creatine kinase Proteins 0.000 description 1
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 102100031780 Endonuclease Human genes 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical compound 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
- 208000010496 Heart Arrest Diseases 0.000 description 1
- 101000889953 Homo sapiens Apolipoprotein B-100 Proteins 0.000 description 1
- 101000908713 Homo sapiens Dihydrofolate reductase Proteins 0.000 description 1
- 108010046315 IDL Lipoproteins Proteins 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 208000031773 Insulin resistance syndrome Diseases 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 101710203526 Integrase Proteins 0.000 description 1
- 206010023126 Jaundice Diseases 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000005736 Nervous System Malformations Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 208000005764 Peripheral Arterial Disease Diseases 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 description 1
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 description 1
- 108010022249 Proprotein Convertase 9 Proteins 0.000 description 1
- 102000012343 Proprotein Convertase 9 Human genes 0.000 description 1
- 108010044159 Proprotein Convertases Proteins 0.000 description 1
- 102000006437 Proprotein Convertases Human genes 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 240000003152 Rhus chinensis Species 0.000 description 1
- 235000014220 Rhus chinensis Nutrition 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 241000239226 Scorpiones Species 0.000 description 1
- 108091027568 Single-stranded nucleotide Proteins 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 241000871311 Toxicodendron vernix Species 0.000 description 1
- 102000003929 Transaminases Human genes 0.000 description 1
- 108090000340 Transaminases Proteins 0.000 description 1
- 206010048215 Xanthomatosis Diseases 0.000 description 1
- PNAMDJVUJCJOIX-IUNFJCKHSA-N [(1s,3r,7s,8s,8ar)-8-[2-[(2r,4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] 2,2-dimethylbutanoate;(3r,4s)-1-(4-fluorophenyl)-3-[(3s)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)azetidin-2-one Chemical group C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1.N1([C@@H]([C@H](C1=O)CC[C@H](O)C=1C=CC(F)=CC=1)C=1C=CC(O)=CC=1)C1=CC=C(F)C=C1 PNAMDJVUJCJOIX-IUNFJCKHSA-N 0.000 description 1
- 208000002223 abdominal aortic aneurysm Diseases 0.000 description 1
- 230000035508 accumulation Effects 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- AMTPYFGPPVFBBI-UHFFFAOYSA-N acedapsone Chemical compound C1=CC(NC(=O)C)=CC=C1S(=O)(=O)C1=CC=C(NC(C)=O)C=C1 AMTPYFGPPVFBBI-UHFFFAOYSA-N 0.000 description 1
- 229950009438 acedapsone Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 229960000643 adenine Drugs 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 125000002431 aminoalkoxy group Chemical group 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 229940030486 androgens Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 229940127226 anticholesterol agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 208000007474 aortic aneurysm Diseases 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000516 bezafibrate Drugs 0.000 description 1
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000004663 bisphosphonates Chemical class 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 206010007625 cardiogenic shock Diseases 0.000 description 1
- 230000003293 cardioprotective effect Effects 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000004700 cellular uptake Effects 0.000 description 1
- 230000002759 chromosomal effect Effects 0.000 description 1
- 229960001152 colesevelam Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000006392 deoxygenation reaction Methods 0.000 description 1
- 239000005549 deoxyribonucleoside Substances 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 229940054572 ezetimibe / simvastatin Drugs 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229960003765 fluvastatin Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229960003627 gemfibrozil Drugs 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000003147 glycosyl group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 235000009200 high fat diet Nutrition 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000000893 inhibin Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000002608 intravascular ultrasound Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 108020001756 ligand binding domains Proteins 0.000 description 1
- 230000006372 lipid accumulation Effects 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 230000007056 liver toxicity Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 108010038232 microsomal triglyceride transfer protein Proteins 0.000 description 1
- 108091060283 mipomersen Proteins 0.000 description 1
- OSGPYAHSKOGBFY-KMHHXCEHSA-A mipomersen sodium Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+].N1([C@H]2C[C@@H]([C@H](O2)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C(C)=C2)=O)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP([O-])(=O)S[C@@H]2[C@H](O[C@H](C2)N2C3=NC=NC(N)=C3N=C2)COP([O-])(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP([O-])(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP([O-])(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP([O-])(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2COP([O-])(=O)S[C@H]2[C@H]([C@@H](O[C@@H]2CO)N2C3=C(C(NC(N)=N3)=O)N=C2)OCCOC)N2C(N=C(N)C(C)=C2)=O)OCCOC)N2C(N=C(N)C(C)=C2)=O)OCCOC)N2C(NC(=O)C(C)=C2)=O)OCCOC)N2C(N=C(N)C(C)=C2)=O)OCCOC)SP([O-])(=O)OC[C@H]2O[C@H](C[C@@H]2SP([O-])(=O)OC[C@H]2O[C@H](C[C@@H]2SP([O-])(=O)OC[C@H]2O[C@H](C[C@@H]2SP([O-])(=O)OC[C@@H]2[C@H]([C@H]([C@@H](O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OCCOC)SP([O-])(=O)OC[C@H]2[C@@H]([C@@H]([C@H](O2)N2C(N=C(N)C(C)=C2)=O)OCCOC)SP([O-])(=O)OC[C@H]2[C@@H]([C@@H]([C@H](O2)N2C3=NC=NC(N)=C3N=C2)OCCOC)SP([O-])(=O)OC[C@H]2[C@@H]([C@@H]([C@H](O2)N2C(N=C(N)C(C)=C2)=O)OCCOC)SP([O-])(=O)OC[C@H]2[C@H](O)[C@@H]([C@H](O2)N2C(N=C(N)C(C)=C2)=O)OCCOC)N2C(N=C(N)C(C)=C2)=O)N2C(NC(=O)C(C)=C2)=O)N2C(NC(=O)C(C)=C2)=O)C=C(C)C(N)=NC1=O OSGPYAHSKOGBFY-KMHHXCEHSA-A 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 235000021084 monounsaturated fats Nutrition 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 208000015001 muscle soreness Diseases 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 230000010807 negative regulation of binding Effects 0.000 description 1
- 125000000627 niacin group Chemical group 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 125000004437 phosphorous atom Chemical group 0.000 description 1
- 229910001392 phosphorus oxide Inorganic materials 0.000 description 1
- 230000037081 physical activity Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 235000002949 phytic acid Nutrition 0.000 description 1
- 239000000467 phytic acid Substances 0.000 description 1
- 229940068041 phytic acid Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 208000030683 polygenic disease Diseases 0.000 description 1
- 235000021085 polyunsaturated fats Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 229960002965 pravastatin Drugs 0.000 description 1
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 description 1
- 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
- 238000002360 preparation method Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
- 239000001397 quillaja saponaria molina bark Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000008085 renal dysfunction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 229930182490 saponin Natural products 0.000 description 1
- 150000007949 saponins Chemical class 0.000 description 1
- 235000021003 saturated fats Nutrition 0.000 description 1
- 231100000241 scar Toxicity 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 description 1
- 229960004425 sibutramine Drugs 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000000472 sulfonyl group Chemical class *S(*)(=O)=O 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000013077 target material Substances 0.000 description 1
- VSAISIQCTGDGPU-UHFFFAOYSA-N tetraphosphorus hexaoxide Chemical compound O1P(O2)OP3OP1OP2O3 VSAISIQCTGDGPU-UHFFFAOYSA-N 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 150000007944 thiolates Chemical class 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000012384 transportation and delivery Methods 0.000 description 1
- 238000012285 ultrasound imaging Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/105—Murine
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/035—Animal model for multifactorial diseases
- A01K2267/0375—Animal model for cardiovascular diseases
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/31—Chemical structure of the backbone
- C12N2310/315—Phosphorothioates
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/321—2'-O-R Modification
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/33—Chemical structure of the base
- C12N2310/334—Modified C
- C12N2310/3341—5-Methylcytosine
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/341—Gapmers, i.e. of the type ===---===
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/34—Spatial arrangement of the modifications
- C12N2310/346—Spatial arrangement of the modifications having a combination of backbone and sugar modifications
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Medicinal Chemistry (AREA)
- General Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Plant Pathology (AREA)
- Biophysics (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Hematology (AREA)
- Virology (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US86739506P | 2006-11-27 | 2006-11-27 | |
| US91289207P | 2007-04-19 | 2007-04-19 | |
| US98628607P | 2007-11-07 | 2007-11-07 | |
| US98807407P | 2007-11-14 | 2007-11-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TW200838551A true TW200838551A (en) | 2008-10-01 |
Family
ID=39276232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW096145015A TW200838551A (en) | 2006-11-27 | 2007-11-27 | Methods for treating hypercholesterolemia |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US8084437B2 (cg-RX-API-DMAC7.html) |
| EP (3) | EP2455471A3 (cg-RX-API-DMAC7.html) |
| JP (1) | JP2010510807A (cg-RX-API-DMAC7.html) |
| KR (1) | KR20090103894A (cg-RX-API-DMAC7.html) |
| AU (1) | AU2007325767A1 (cg-RX-API-DMAC7.html) |
| CA (1) | CA2670563A1 (cg-RX-API-DMAC7.html) |
| CO (1) | CO6241169A2 (cg-RX-API-DMAC7.html) |
| EA (1) | EA200900741A1 (cg-RX-API-DMAC7.html) |
| IL (1) | IL198851A0 (cg-RX-API-DMAC7.html) |
| MX (1) | MX2009005527A (cg-RX-API-DMAC7.html) |
| NO (1) | NO20092150L (cg-RX-API-DMAC7.html) |
| TW (1) | TW200838551A (cg-RX-API-DMAC7.html) |
| WO (1) | WO2008066776A2 (cg-RX-API-DMAC7.html) |
Families Citing this family (56)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2835429B1 (en) | 2006-05-11 | 2017-12-13 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of the PCSK9 gene |
| US8084437B2 (en) | 2006-11-27 | 2011-12-27 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| US8093222B2 (en) | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| JOP20080381B1 (ar) | 2007-08-23 | 2023-03-28 | Amgen Inc | بروتينات مرتبطة بمولدات مضادات تتفاعل مع بروبروتين كونفيرتاز سيتيليزين ككسين من النوع 9 (pcsk9) |
| AU2009213147A1 (en) | 2008-02-11 | 2009-08-20 | Rxi Pharmaceuticals Corp. | Modified RNAi polynucleotides and uses thereof |
| WO2009148605A2 (en) * | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| DK2379084T3 (en) * | 2008-10-15 | 2018-01-22 | Ionis Pharmaceuticals Inc | MODULATION OF FACTOR 11 EXPRESSION |
| AU2009323766B2 (en) | 2008-12-02 | 2016-10-06 | Wave Life Sciences Ltd. | Method for the synthesis of phosphorus atom modified nucleic acids |
| JO3672B1 (ar) | 2008-12-15 | 2020-08-27 | Regeneron Pharma | أجسام مضادة بشرية عالية التفاعل الكيماوي بالنسبة لإنزيم سبتيليسين كنفرتيز بروبروتين / كيكسين نوع 9 (pcsk9). |
| US9493774B2 (en) * | 2009-01-05 | 2016-11-15 | Rxi Pharmaceuticals Corporation | Inhibition of PCSK9 through RNAi |
| CA2754043A1 (en) * | 2009-03-12 | 2010-09-16 | Alnylam Pharmaceuticals, Inc. | Lipid formulated compositions and methods for inhibiting expression of eg5 and vegf genes |
| BRPI1015236A2 (pt) * | 2009-04-15 | 2019-09-24 | Isis Pharmaceuticals Inc | métodos para modular uma resposta inflamatória, apra melhorar uma doença, distúrbio ou condição inflamatórios em um animal, para tratar um animal em risco para uma doença, distúrbio ou condição inflamatórios, para inibir a expressão de fator xi em um animal, para reduzir o risco de doença, distúrbio ou condição inflamatórios, em um animal, para tratar um animal em risco para uma doença inflamatória, e para tratar um animal tendo uma doença inflamatória, e, uso de um composto marcado para fator xi |
| NZ597504A (en) | 2009-06-15 | 2013-10-25 | Alnylam Pharmaceuticals Inc | Lipid formulated dsrna targeting the pcsk9 gene |
| US9051567B2 (en) | 2009-06-15 | 2015-06-09 | Tekmira Pharmaceuticals Corporation | Methods for increasing efficacy of lipid formulated siRNA |
| SG177564A1 (en) | 2009-07-06 | 2012-02-28 | Ontorii Inc | Novel nucleic acid prodrugs and methods of use thereof |
| EP2456870A1 (en) * | 2009-07-21 | 2012-05-30 | Santaris Pharma A/S | Antisense oligomers targeting pcsk9 |
| EP3321361B1 (en) * | 2010-02-08 | 2019-03-27 | Ionis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
| WO2011097644A2 (en) | 2010-02-08 | 2011-08-11 | Isis Pharmaceuticals, Inc. | Selective reduction of allelic variants |
| GB2481373A (en) * | 2010-06-21 | 2011-12-28 | Weiming Xu | Treatment of hypercholesterolaemia by ubiquitination of PCSK9 |
| EP2620428B1 (en) | 2010-09-24 | 2019-05-22 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
| EP2633046A4 (en) * | 2010-10-29 | 2015-05-06 | Alnylam Pharmaceuticals Inc | COMPOSITIONS AND METHODS FOR INHIBITING PCSK9 GENES |
| AR084938A1 (es) | 2011-01-28 | 2013-07-10 | Sanofi Sa | Anticuerpos humanos contra la proproteina convertasa subtilisina/kexina tipo 9 (anti pcsk9) para usar en metodos para tratar grupos de pacientes |
| US9605019B2 (en) | 2011-07-19 | 2017-03-28 | Wave Life Sciences Ltd. | Methods for the synthesis of functionalized nucleic acids |
| AR087305A1 (es) | 2011-07-28 | 2014-03-12 | Regeneron Pharma | Formulaciones estabilizadas que contienen anticuerpos anti-pcsk9, metodo de preparacion y kit |
| DK2742135T4 (da) | 2011-08-11 | 2020-07-13 | Ionis Pharmaceuticals Inc | Bindingsmodificerede gapped oligomeriske forbindelser og anvendelser deraf |
| ES2773111T3 (es) | 2011-09-16 | 2020-07-09 | Regeneron Pharma | Inhibidor de la proproteína convertasa subtilisina/kexina 9 (PCSK9) para su uso en la reducción de los niveles de lipoproteína (a) |
| AR091462A1 (es) | 2012-06-15 | 2015-02-04 | Genentech Inc | Anticuerpos anti-pcsk9, formulaciones, dosificacion y metodos de uso |
| JP2015165772A (ja) * | 2012-07-04 | 2015-09-24 | 国立大学法人大阪大学 | オリゴヌクレオチド、およびオリゴヌクレオチドを有効成分として含有する脂質異常症治療剤 |
| JP6268157B2 (ja) | 2012-07-13 | 2018-01-24 | 株式会社Ｗａｖｅ Ｌｉｆｅ Ｓｃｉｅｎｃｅｓ Ｊａｐａｎ | 不斉補助基 |
| JP6246121B2 (ja) | 2012-07-13 | 2017-12-13 | 株式会社新日本科学 | キラル核酸アジュバント |
| SG10201912895PA (en) | 2012-07-13 | 2020-02-27 | Wave Life Sciences Ltd | Chiral control |
| EP3459549B1 (en) | 2012-10-12 | 2022-04-06 | Ionis Pharmaceuticals, Inc. | Selective antisense compounds and uses thereof |
| ES2724853T3 (es) | 2012-11-15 | 2019-09-16 | Roche Innovation Ct Copenhagen As | Conjugados de oligonucleótidos |
| PT2929031T (pt) | 2012-12-05 | 2018-01-19 | Alnylam Pharmaceuticals Inc | Composições de irna de pcsk9 e métodos de seu uso |
| MY177989A (en) | 2013-01-30 | 2020-09-28 | Hoffmann La Roche | Lna oligonucleotide carbohydrate conjugates |
| GB2523527A (en) * | 2013-04-05 | 2015-09-02 | Weiming Xu | Screen compounds for the modulation of proprotein convertase subtilisin/kexin type 9(PCSK9) |
| MX2015014666A (es) | 2013-04-17 | 2016-03-01 | Pfizer | Derivados de n-piperidin-3-ilbenzamida para tratar enfermedades cardiovasculares. |
| KR102138781B1 (ko) | 2013-05-01 | 2020-07-28 | 아이오니스 파마수티컬즈, 인코포레이티드 | 아포지질단백질 c-iii 발현을 조절하는 조성물 및 방법 |
| US10111953B2 (en) | 2013-05-30 | 2018-10-30 | Regeneron Pharmaceuticals, Inc. | Methods for reducing remnant cholesterol and other lipoprotein fractions by administering an inhibitor of proprotein convertase subtilisin kexin-9 (PCSK9) |
| SG10201908122XA (en) | 2013-06-27 | 2019-10-30 | Roche Innovation Ct Copenhagen As | Antisense oligomers and conjugates targeting pcsk9 |
| JP6487913B2 (ja) * | 2013-07-02 | 2019-03-20 | アイオーニス ファーマシューティカルズ， インコーポレーテッドＩｏｎｉｓ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | 成長ホルモン受容体のモジュレータ |
| JPWO2015108047A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 免疫誘導活性を有するキラル核酸アジュバンド及び免疫誘導活性剤 |
| JPWO2015108048A1 (ja) | 2014-01-15 | 2017-03-23 | 株式会社新日本科学 | 抗腫瘍作用を有するキラル核酸アジュバンド及び抗腫瘍剤 |
| EP3095460A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
| PT3094728T (pt) | 2014-01-16 | 2022-05-19 | Wave Life Sciences Ltd | Desenho quiral |
| WO2015179693A1 (en) | 2014-05-22 | 2015-11-26 | Isis Pharmaceuticals, Inc. | Conjugated antisense compounds and their use |
| CN109477106B (zh) * | 2015-07-10 | 2022-10-04 | Ionis制药公司 | 二酰基甘油酰基转移酶2(dgat2)的调节剂 |
| EA201890519A1 (ru) | 2015-08-18 | 2018-07-31 | Ридженерон Фармасьютикалз, Инк. | Ингибирующие антитела против pcsk9 для лечения пациентов с гиперлипидемией, подвергающихся аферезу липопротеинов |
| KR102793532B1 (ko) | 2015-08-25 | 2025-04-14 | 알닐람 파마슈티칼스 인코포레이티드 | 전구단백질 컨버타제 서브틸리신 켁신 (pcsk9) 유전자-관련 장애를 치료하기 위한 방법 및 조성물 |
| US11400161B2 (en) | 2016-10-06 | 2022-08-02 | Ionis Pharmaceuticals, Inc. | Method of conjugating oligomeric compounds |
| JP2019535839A (ja) | 2016-11-29 | 2019-12-12 | ピュアテック ヘルス エルエルシー | 治療剤の送達のためのエクソソーム |
| JOP20190215A1 (ar) * | 2017-03-24 | 2019-09-19 | Ionis Pharmaceuticals Inc | مُعدّلات التعبير الوراثي عن pcsk9 |
| KR102749200B1 (ko) * | 2018-04-18 | 2025-01-03 | 다이서나 파마수이티컬, 인크. | 고콜레스테롤혈증 및 관련 상태를 치료하기 위한 pcsk9 표적화 올리고뉴클레오티드 |
| CR20200605A (es) | 2018-05-09 | 2021-01-29 | Ionis Pharmaceuticals Inc | Compuestos y métodos para la reducción de la expresión de fxi |
| KR20180087217A (ko) | 2018-07-20 | 2018-08-01 | 주식회사 유진바이오텍 | 귀리산화 베타-글루칸을 유효성분으로 포함하는 비만, 이상지방혈증(dyslipidemia) 또는 지방간의 예방 또는 치료용 조성물 |
| WO2024229020A2 (en) * | 2023-05-01 | 2024-11-07 | Chroma Medicine, Inc. | Compositions and methods for epigenetic regulation of pcsk9 expression |
Family Cites Families (84)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US604360A (en) * | 1898-05-24 | Safety device for elevators | ||
| US5023243A (en) | 1981-10-23 | 1991-06-11 | Molecular Biosystems, Inc. | Oligonucleotide therapeutic agent and method of making same |
| US5118800A (en) | 1983-12-20 | 1992-06-02 | California Institute Of Technology | Oligonucleotides possessing a primary amino group in the terminal nucleotide |
| FR2567892B1 (fr) | 1984-07-19 | 1989-02-17 | Centre Nat Rech Scient | Nouveaux oligonucleotides, leur procede de preparation et leurs applications comme mediateurs dans le developpement des effets des interferons |
| US5591722A (en) | 1989-09-15 | 1997-01-07 | Southern Research Institute | 2'-deoxy-4'-thioribonucleosides and their antiviral activity |
| JPH05504552A (ja) | 1989-10-24 | 1993-07-15 | ギリアド サイエンシズ，インコーポレイテッド | ２’位が改変されたオリゴヌクレオチド |
| US5646265A (en) | 1990-01-11 | 1997-07-08 | Isis Pharmceuticals, Inc. | Process for the preparation of 2'-O-alkyl purine phosphoramidites |
| US5681941A (en) | 1990-01-11 | 1997-10-28 | Isis Pharmaceuticals, Inc. | Substituted purines and oligonucleotide cross-linking |
| US6005087A (en) | 1995-06-06 | 1999-12-21 | Isis Pharmaceuticals, Inc. | 2'-modified oligonucleotides |
| US5670633A (en) | 1990-01-11 | 1997-09-23 | Isis Pharmaceuticals, Inc. | Sugar modified oligonucleotides that detect and modulate gene expression |
| GB9009980D0 (en) | 1990-05-03 | 1990-06-27 | Amersham Int Plc | Phosphoramidite derivatives,their preparation and the use thereof in the incorporation of reporter groups on synthetic oligonucleotides |
| DK0455905T3 (da) | 1990-05-11 | 1998-12-07 | Microprobe Corp | Dipsticks til nukleinsyrehybridiseringsassays og fremgangsmåde til kovalent immobilisering af oligonukleotider |
| US5677437A (en) | 1990-07-27 | 1997-10-14 | Isis Pharmaceuticals, Inc. | Heteroatomic oligonucleoside linkages |
| IL113519A (en) | 1990-08-03 | 1997-11-20 | Sterling Winthrop Inc | Oligonucleoside sequences of from about 6 to about 200 bases having a three atom internucleoside linkage, their preparation and pharmaceutical compositions for inhibiting gene expression containing said oligonucleosides |
| US6582908B2 (en) | 1990-12-06 | 2003-06-24 | Affymetrix, Inc. | Oligonucleotides |
| ES2103918T3 (es) | 1991-10-17 | 1997-10-01 | Ciba Geigy Ag | Nucleosidos biciclicos, oligonucleotidos, procedimiento para su obtencion y productos intermedios. |
| TW393513B (en) | 1991-11-26 | 2000-06-11 | Isis Pharmaceuticals Inc | Enhanced triple-helix and double-helix formation with oligomers containing modified pyrimidines |
| US5359044A (en) | 1991-12-13 | 1994-10-25 | Isis Pharmaceuticals | Cyclobutyl oligonucleotide surrogates |
| FR2687679B1 (fr) | 1992-02-05 | 1994-10-28 | Centre Nat Rech Scient | Oligothionucleotides. |
| US5633360A (en) | 1992-04-14 | 1997-05-27 | Gilead Sciences, Inc. | Oligonucleotide analogs capable of passive cell membrane permeation |
| EP0577558A2 (de) | 1992-07-01 | 1994-01-05 | Ciba-Geigy Ag | Carbocyclische Nukleoside mit bicyclischen Ringen, Oligonukleotide daraus, Verfahren zu deren Herstellung, deren Verwendung und Zwischenproduckte |
| WO1994001093A1 (en) | 1992-07-09 | 1994-01-20 | Merck & Co., Inc. | Controlled porosity osmotic enalapril pump |
| US5652355A (en) | 1992-07-23 | 1997-07-29 | Worcester Foundation For Experimental Biology | Hybrid oligonucleotide phosphorothioates |
| DK0691968T3 (da) | 1993-03-30 | 1998-02-23 | Sanofi Sa | Acykliske nukleosid-analoge og oligonukleotidsekvenser indeholdende disse |
| WO1994022891A1 (en) | 1993-03-31 | 1994-10-13 | Sterling Winthrop Inc. | Oligonucleotides with amide linkages replacing phosphodiester linkages |
| WO1994022890A1 (en) | 1993-03-31 | 1994-10-13 | Sterling Winthop Inc. | Novel 5'-substituted nucleosides and oligomers produced therefrom |
| DE4311944A1 (de) | 1993-04-10 | 1994-10-13 | Degussa | Umhüllte Natriumpercarbonatpartikel, Verfahren zu deren Herstellung und sie enthaltende Wasch-, Reinigungs- und Bleichmittelzusammensetzungen |
| US5801154A (en) | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
| US5457187A (en) | 1993-12-08 | 1995-10-10 | Board Of Regents University Of Nebraska | Oligonucleotides containing 5-fluorouracil |
| US5446137B1 (en) | 1993-12-09 | 1998-10-06 | Behringwerke Ag | Oligonucleotides containing 4'-substituted nucleotides |
| US5519134A (en) | 1994-01-11 | 1996-05-21 | Isis Pharmaceuticals, Inc. | Pyrrolidine-containing monomers and oligomers |
| US5627053A (en) | 1994-03-29 | 1997-05-06 | Ribozyme Pharmaceuticals, Inc. | 2'deoxy-2'-alkylnucleotide containing nucleic acid |
| US5625050A (en) | 1994-03-31 | 1997-04-29 | Amgen Inc. | Modified oligonucleotides and intermediates useful in nucleic acid therapeutics |
| US5597909A (en) | 1994-08-25 | 1997-01-28 | Chiron Corporation | Polynucleotide reagents containing modified deoxyribose moieties, and associated methods of synthesis and use |
| US5792747A (en) | 1995-01-24 | 1998-08-11 | The Administrators Of The Tulane Educational Fund | Highly potent agonists of growth hormone releasing hormone |
| US5567427A (en) * | 1995-03-17 | 1996-10-22 | Helene Curtis, Inc. | Emulsified, low ph cosmetic compositions having improved stability |
| US5673633A (en) * | 1995-05-31 | 1997-10-07 | Pfister; Joel W. | Table leg system |
| ES2192672T3 (es) | 1996-11-18 | 2003-10-16 | Takeshi Imanishi | Nuevos analogos de nucleotidos. |
| JP3756313B2 (ja) | 1997-03-07 | 2006-03-15 | 武 今西 | 新規ビシクロヌクレオシド及びオリゴヌクレオチド類縁体 |
| US6770748B2 (en) | 1997-03-07 | 2004-08-03 | Takeshi Imanishi | Bicyclonucleoside and oligonucleotide analogue |
| JP4236812B2 (ja) | 1997-09-12 | 2009-03-11 | エクシコン エ／エス | オリゴヌクレオチド類似体 |
| US6794499B2 (en) | 1997-09-12 | 2004-09-21 | Exiqon A/S | Oligonucleotide analogues |
| US20030228597A1 (en) | 1998-04-13 | 2003-12-11 | Cowsert Lex M. | Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation |
| US6043352A (en) | 1998-08-07 | 2000-03-28 | Isis Pharmaceuticals, Inc. | 2'-O-Dimethylaminoethyloxyethyl-modified oligonucleotides |
| US6410323B1 (en) | 1999-08-31 | 2002-06-25 | Isis Pharmaceuticals, Inc. | Antisense modulation of human Rho family gene expression |
| ATE287897T2 (de) | 1999-02-12 | 2005-02-15 | Sankyo Co | Analoga von nukleosiden und oligonukleotiden |
| US7084125B2 (en) | 1999-03-18 | 2006-08-01 | Exiqon A/S | Xylo-LNA analogues |
| CN102180924A (zh) | 1999-05-04 | 2011-09-14 | 桑塔里斯制药公司 | L-核糖-lna类似物 |
| US6525191B1 (en) | 1999-05-11 | 2003-02-25 | Kanda S. Ramasamy | Conformationally constrained L-nucleosides |
| JP4151751B2 (ja) | 1999-07-22 | 2008-09-17 | 第一三共株式会社 | 新規ビシクロヌクレオシド類縁体 |
| AU2001282522A1 (en) | 2000-08-29 | 2002-03-13 | Takeshi Imanishi | Novel nucleoside analogs and oligonucleotide derivatives containing these analogs |
| US6426220B1 (en) | 2000-10-30 | 2002-07-30 | Isis Pharmaceuticals, Inc. | Antisense modulation of calreticulin expression |
| WO2003004602A2 (en) | 2001-07-03 | 2003-01-16 | Isis Pharmaceuticals, Inc. | Nuclease resistant chimeric oligonucleotides |
| US7407943B2 (en) | 2001-08-01 | 2008-08-05 | Isis Pharmaceuticals, Inc. | Antisense modulation of apolipoprotein B expression |
| US7060809B2 (en) | 2001-09-04 | 2006-06-13 | Exiqon A/S | LNA compositions and uses thereof |
| EP1501930A2 (en) | 2002-04-05 | 2005-02-02 | Santaris Pharma A/S | Oligomeric compounds for the modulation hif-1alpha expression |
| US7569575B2 (en) | 2002-05-08 | 2009-08-04 | Santaris Pharma A/S | Synthesis of locked nucleic acid derivatives |
| US20040219565A1 (en) | 2002-10-21 | 2004-11-04 | Sakari Kauppinen | Oligonucleotides useful for detecting and analyzing nucleic acids of interest |
| EP1562971B1 (en) | 2002-11-05 | 2014-02-12 | Isis Pharmaceuticals, Inc. | Polycyclic sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation |
| US7511131B2 (en) | 2002-11-13 | 2009-03-31 | Genzyme Corporation | Antisense modulation of apolipoprotein B expression |
| US7655785B1 (en) | 2002-11-14 | 2010-02-02 | Rosetta Genomics Ltd. | Bioinformatically detectable group of novel regulatory oligonucleotides and uses thereof |
| EP2314691A3 (en) | 2002-11-14 | 2012-01-18 | Dharmacon, Inc. | Fuctional and hyperfunctional siRNA |
| ATE442152T1 (de) | 2002-11-18 | 2009-09-15 | Santaris Pharma As | Antisense-entwurf |
| JP2004357715A (ja) * | 2003-01-21 | 2004-12-24 | Research Association For Biotechnology | 全長ｃＤＮＡ |
| EP1471152A1 (en) * | 2003-04-25 | 2004-10-27 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Mutations in the human PCSK9 gene associated to hypercholesterolemia |
| JP2005060664A (ja) | 2003-07-31 | 2005-03-10 | Asahi Glass Co Ltd | 含フッ素化合物、含フッ素ポリマーとその製造方法およびそれを含むレジスト組成物 |
| US7427672B2 (en) | 2003-08-28 | 2008-09-23 | Takeshi Imanishi | Artificial nucleic acids of n-o bond crosslinkage type |
| EP1766071A4 (en) | 2004-06-03 | 2009-11-11 | Isis Pharmaceuticals Inc | DOUBLE-STRONG COMPOSITIONS WITH DIFFERENTLY MODIFIED STRANDS FOR USE IN GENE MODULATION |
| WO2006085973A2 (en) | 2004-07-02 | 2006-08-17 | Avi Biopharma, Inc. | Antisense antibacterial method and compound |
| WO2006126040A1 (en) | 2005-05-25 | 2006-11-30 | Rosetta Genomics Ltd. | Bacterial and bacterial associated mirnas and uses thereof |
| US20070068404A1 (en) | 2005-09-29 | 2007-03-29 | Edwin Hirahara | Systems and methods for additive deposition of materials onto a substrate |
| JP5128796B2 (ja) | 2006-01-20 | 2013-01-23 | Ｇ＆Ｇサイエンス株式会社 | 脳血管障害の遺伝的リスク検出法 |
| CN102908630B (zh) | 2006-01-27 | 2014-11-19 | Isis制药公司 | 6-修饰的双环核酸类似物 |
| EP2015758B1 (en) | 2006-05-05 | 2014-04-02 | Isis Pharmaceuticals, Inc. | Compounds and methods for modulating expression apob |
| EP2835429B1 (en) * | 2006-05-11 | 2017-12-13 | Alnylam Pharmaceuticals Inc. | Compositions and methods for inhibiting expression of the PCSK9 gene |
| US7572618B2 (en) | 2006-06-30 | 2009-08-11 | Bristol-Myers Squibb Company | Polynucleotides encoding novel PCSK9 variants |
| CA2658183A1 (en) | 2006-07-17 | 2008-01-24 | Sirna Therapeutics Inc. | Rna interference mediated inhibition of proprotein convertase subtilisin kexin 9 (pcsk9) gene expression using short interfering nucleic acid (sina) |
| EP2076597A2 (en) * | 2006-10-09 | 2009-07-08 | Santaris Pharma A/S | Rna antagonist compounds for the modulation of pcsk9 |
| AU2007306542B2 (en) | 2006-10-11 | 2013-08-01 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Influenza targets |
| US8084437B2 (en) | 2006-11-27 | 2011-12-27 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| US8093222B2 (en) * | 2006-11-27 | 2012-01-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
| US20100105134A1 (en) | 2007-03-02 | 2010-04-29 | Mdrna, Inc. | Nucleic acid compounds for inhibiting gene expression and uses thereof |
| WO2008109369A2 (en) | 2007-03-02 | 2008-09-12 | Mdrna, Inc. | Nucleic acid compounds for inhibiting tnf gene expression and uses thereof |
| WO2009148605A2 (en) | 2008-06-04 | 2009-12-10 | Isis Pharmaceuticals, Inc. | Methods for treating hypercholesterolemia |
-
2007
- 2007-11-27 US US12/516,457 patent/US8084437B2/en active Active
- 2007-11-27 MX MX2009005527A patent/MX2009005527A/es not_active Application Discontinuation
- 2007-11-27 EP EP11192458A patent/EP2455471A3/en not_active Withdrawn
- 2007-11-27 CA CA002670563A patent/CA2670563A1/en not_active Abandoned
- 2007-11-27 EA EA200900741A patent/EA200900741A1/ru unknown
- 2007-11-27 EP EP07862213A patent/EP2102340A2/en not_active Withdrawn
- 2007-11-27 AU AU2007325767A patent/AU2007325767A1/en not_active Abandoned
- 2007-11-27 WO PCT/US2007/024369 patent/WO2008066776A2/en not_active Ceased
- 2007-11-27 TW TW096145015A patent/TW200838551A/zh unknown
- 2007-11-27 EP EP11192464A patent/EP2453016A1/en not_active Withdrawn
- 2007-11-27 KR KR1020097013295A patent/KR20090103894A/ko not_active Withdrawn
- 2007-11-27 JP JP2009539274A patent/JP2010510807A/ja active Pending
-
2009
- 2009-05-20 IL IL198851A patent/IL198851A0/en unknown
- 2009-06-03 NO NO20092150A patent/NO20092150L/no not_active Application Discontinuation
- 2009-06-26 CO CO09066682A patent/CO6241169A2/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NO20092150L (no) | 2009-07-31 |
| EP2455471A2 (en) | 2012-05-23 |
| EA200900741A1 (ru) | 2010-04-30 |
| CO6241169A2 (es) | 2011-01-20 |
| AU2007325767A1 (en) | 2008-06-05 |
| AU2007325767A2 (en) | 2009-07-09 |
| WO2008066776A3 (en) | 2008-09-25 |
| US20100144834A1 (en) | 2010-06-10 |
| WO2008066776A2 (en) | 2008-06-05 |
| EP2453016A1 (en) | 2012-05-16 |
| CA2670563A1 (en) | 2008-06-05 |
| US8084437B2 (en) | 2011-12-27 |
| KR20090103894A (ko) | 2009-10-01 |
| EP2455471A3 (en) | 2012-09-12 |
| MX2009005527A (es) | 2009-06-08 |
| EP2102340A2 (en) | 2009-09-23 |
| JP2010510807A (ja) | 2010-04-08 |
| IL198851A0 (en) | 2011-08-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| TW200838551A (en) | Methods for treating hypercholesterolemia | |
| US20250313843A1 (en) | Methods for treating hypercholesterolemia | |
| JP6440592B2 (ja) | アンジオポエチン様３発現の調節 | |
| CN104302654B (zh) | 用于调节载脂蛋白(a)表达的方法和组合物 | |
| KR102169899B1 (ko) | 지질단백질 리파제 결핍 (lpld) 모집단에서 아포지질단백질 c-iii (apociii) 발현의 조절 | |
| WO2009148605A2 (en) | Methods for treating hypercholesterolemia | |
| CN107714715A (zh) | 载脂蛋白ciii（apociii）表达的调节 | |
| JP2021185149A (ja) | アポリポタンパク質（ａ）発現の調節 | |
| RU2737719C2 (ru) | Модулирование экспрессии аполипопротеина с-iii (аросiii) у пациентов с липодистрофией |