JPWO2020257631A5 - - Google Patents
Download PDFInfo
- Publication number
- JPWO2020257631A5 JPWO2020257631A5 JP2021576065A JP2021576065A JPWO2020257631A5 JP WO2020257631 A5 JPWO2020257631 A5 JP WO2020257631A5 JP 2021576065 A JP2021576065 A JP 2021576065A JP 2021576065 A JP2021576065 A JP 2021576065A JP WO2020257631 A5 JPWO2020257631 A5 JP WO2020257631A5
- Authority
- JP
- Japan
- Prior art keywords
- patient
- seq
- disease
- oligonucleotide
- optionally
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 108091034117 Oligonucleotide Proteins 0.000 claims description 155
- 238000000034 method Methods 0.000 claims description 134
- 208000012902 Nervous system disease Diseases 0.000 claims description 90
- 208000025966 Neurological disease Diseases 0.000 claims description 85
- 239000002777 nucleoside Substances 0.000 claims description 84
- 239000008194 pharmaceutical composition Substances 0.000 claims description 64
- 102100022343 Protein phosphatase 1A Human genes 0.000 claims description 60
- 101000620650 Homo sapiens Protein phosphatase 1A Proteins 0.000 claims description 56
- 201000001119 neuropathy Diseases 0.000 claims description 56
- 230000007823 neuropathy Effects 0.000 claims description 56
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 54
- -1 for example Chemical compound 0.000 claims description 42
- 125000003835 nucleoside group Chemical group 0.000 claims description 40
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 39
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 claims description 37
- 210000004027 cell Anatomy 0.000 claims description 34
- 239000003112 inhibitor Substances 0.000 claims description 34
- 239000002773 nucleotide Substances 0.000 claims description 32
- 125000003729 nucleotide group Chemical group 0.000 claims description 32
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 28
- 229940124597 therapeutic agent Drugs 0.000 claims description 25
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 22
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 22
- 108020004707 nucleic acids Proteins 0.000 claims description 21
- 102000039446 nucleic acids Human genes 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 21
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 claims description 20
- 201000004331 Henoch-Schoenlein purpura Diseases 0.000 claims description 20
- 206010019617 Henoch-Schonlein purpura Diseases 0.000 claims description 20
- 101001111338 Homo sapiens Neurofilament heavy polypeptide Proteins 0.000 claims description 20
- 208000031814 IgA Vasculitis Diseases 0.000 claims description 20
- 102100024007 Neurofilament heavy polypeptide Human genes 0.000 claims description 20
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims description 20
- 208000015446 immunoglobulin a vasculitis Diseases 0.000 claims description 20
- 201000008319 inclusion body myositis Diseases 0.000 claims description 20
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 20
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 19
- 208000024827 Alzheimer disease Diseases 0.000 claims description 18
- 208000018737 Parkinson disease Diseases 0.000 claims description 18
- 230000000295 complement effect Effects 0.000 claims description 18
- 208000010577 Niemann-Pick disease type C Diseases 0.000 claims description 17
- 208000007930 Type C Niemann-Pick Disease Diseases 0.000 claims description 17
- 238000000554 physical therapy Methods 0.000 claims description 17
- 238000001584 occupational therapy Methods 0.000 claims description 16
- 150000007523 nucleic acids Chemical class 0.000 claims description 15
- 150000004713 phosphodiesters Chemical class 0.000 claims description 14
- 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 13
- 238000002560 therapeutic procedure Methods 0.000 claims description 13
- 102000014461 Ataxins Human genes 0.000 claims description 12
- 108010078286 Ataxins Proteins 0.000 claims description 12
- 206010008025 Cerebellar ataxia Diseases 0.000 claims description 12
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 claims description 12
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 claims description 12
- 239000005549 deoxyribonucleoside Substances 0.000 claims description 12
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 12
- 230000000638 stimulation Effects 0.000 claims description 12
- 208000009796 Gangliosidoses Diseases 0.000 claims description 10
- 208000015872 Gaucher disease Diseases 0.000 claims description 10
- 206010019196 Head injury Diseases 0.000 claims description 10
- 101000979333 Homo sapiens Neurofilament light polypeptide Proteins 0.000 claims description 10
- 101000665442 Homo sapiens Serine/threonine-protein kinase TBK1 Proteins 0.000 claims description 10
- 208000023105 Huntington disease Diseases 0.000 claims description 10
- 208000008955 Mucolipidoses Diseases 0.000 claims description 10
- 208000024839 Mucopolysaccharidosis type 2, severe form Diseases 0.000 claims description 10
- 102100023057 Neurofilament light polypeptide Human genes 0.000 claims description 10
- 102100038192 Serine/threonine-protein kinase TBK1 Human genes 0.000 claims description 10
- 238000002512 chemotherapy Methods 0.000 claims description 10
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims description 10
- QPJBWNIQKHGLAU-IQZHVAEDSA-N ganglioside GM1 Chemical compound O[C@@H]1[C@@H](O)[C@H](OC[C@H](NC(=O)CCCCCCCCCCCCCCCCC)[C@H](O)\C=C\CCCCCCCCCCCCC)O[C@H](CO)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@]2(O[C@H]([C@H](NC(C)=O)[C@@H](O)C2)[C@H](O)[C@H](O)CO)C(O)=O)[C@@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)[C@@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](CO)O1 QPJBWNIQKHGLAU-IQZHVAEDSA-N 0.000 claims description 10
- 208000033541 severe form mucopolysaccharidosis type 2 Diseases 0.000 claims description 10
- 208000020431 spinal cord injury Diseases 0.000 claims description 10
- 102100040347 TAR DNA-binding protein 43 Human genes 0.000 claims description 9
- 201000002273 mucopolysaccharidosis II Diseases 0.000 claims description 9
- 208000022018 mucopolysaccharidosis type 2 Diseases 0.000 claims description 9
- NFFPKRVXIPSSQR-BXXZVTAOSA-N (2r,3r,4r)-2,3,4,5-tetrahydroxypentanamide Chemical compound NC(=O)[C@H](O)[C@H](O)[C@H](O)CO NFFPKRVXIPSSQR-BXXZVTAOSA-N 0.000 claims description 8
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 claims description 8
- 208000010886 Peripheral nerve injury Diseases 0.000 claims description 8
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims description 8
- 239000001961 anticonvulsive agent Substances 0.000 claims description 8
- 239000002215 arabinonucleoside Substances 0.000 claims description 8
- 235000017471 coenzyme Q10 Nutrition 0.000 claims description 8
- 229940110767 coenzyme Q10 Drugs 0.000 claims description 8
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 claims description 8
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims description 8
- 238000002630 speech therapy Methods 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 claims description 6
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 6
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 6
- SPUUKOIOZNVGHK-UHFFFAOYSA-N SSSSSSSSSSSSSSS Chemical compound SSSSSSSSSSSSSSS SPUUKOIOZNVGHK-UHFFFAOYSA-N 0.000 claims description 6
- 229940125681 anticonvulsant agent Drugs 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- 210000004556 brain Anatomy 0.000 claims description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 229960002866 duloxetine Drugs 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- 238000007913 intrathecal administration Methods 0.000 claims description 6
- 229910052744 lithium Inorganic materials 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 229960003089 pramipexole Drugs 0.000 claims description 6
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 claims description 6
- 229960004136 rivastigmine Drugs 0.000 claims description 6
- 229960001879 ropinirole Drugs 0.000 claims description 6
- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 claims description 6
- 229960003179 rotigotine Drugs 0.000 claims description 6
- KFQYTPMOWPVWEJ-INIZCTEOSA-N rotigotine Chemical compound CCCN([C@@H]1CC2=CC=CC(O)=C2CC1)CCC1=CC=CS1 KFQYTPMOWPVWEJ-INIZCTEOSA-N 0.000 claims description 6
- FDTAUJJRHBRHIJ-FDJAAIFISA-N tpi-287 Chemical compound O([C@@H]1[C@]2(O)C[C@@H](C(=C([C@H](OC(C)=O)[C@@H]3OC(O[C@H]4C[C@H]5OC[C@]5([C@@H]1[C@]34C)OC(C)=O)C=C)C2(C)C)C)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)CC(C)C)C(=O)C1=CC=CC=C1 FDTAUJJRHBRHIJ-FDJAAIFISA-N 0.000 claims description 6
- 101710150875 TAR DNA-binding protein 43 Proteins 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 230000004048 modification Effects 0.000 claims description 5
- 238000012986 modification Methods 0.000 claims description 5
- 230000004083 survival effect Effects 0.000 claims description 5
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 claims description 4
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 4
- JDXCOXKBIGBZSK-PSNKNOTQSA-N (2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,5S,8S,11S,14S,22S)-22-acetamido-11-benzyl-8-(3-carbamimidamidopropyl)-5-(2-carboxyethyl)-3,6,9,12,16,23-hexaoxo-2-propan-2-yl-1,4,7,10,13,17-hexazacyclotricosane-14-carbonyl]-methylamino]-3-carboxypropanoyl]amino]-3,3-dimethylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-(1H-pyrrolo[2,3-b]pyridin-3-yl)propanoyl]amino]-4-carboxybutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-2-cyclohexylacetyl]amino]-6-[3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[[(4S)-4-carboxy-4-(hexadecanoylamino)butanoyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]hexanoic acid Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCCC[C@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](Cc1c[nH]c2ncccc12)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)N(C)C(=O)[C@@H]1CC(=O)NCCCC[C@H](NC(C)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](Cc2ccccc2)C(=O)N1)C(C)(C)C)C1CCCCC1)C(O)=O)C(O)=O JDXCOXKBIGBZSK-PSNKNOTQSA-N 0.000 claims description 4
- BOOOLEGQBVUTKC-NVQSDHBMSA-N (2e,4e)-3-methyl-5-[(1s,2s)-2-methyl-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)cyclopropyl]penta-2,4-dienoic acid Chemical compound OC(=O)\C=C(/C)\C=C\[C@@H]1C[C@]1(C)C1=CC=C2C(C)(C)CCC(C)(C)C2=C1 BOOOLEGQBVUTKC-NVQSDHBMSA-N 0.000 claims description 4
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 claims description 4
- ZPPUMAMZIMPJGP-UHFFFAOYSA-N 2-methyl-2-[3-methyl-4-[[4-(methylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]pyrazol-1-yl]propanenitrile Chemical compound C1=C(C(F)(F)F)C(NC)=NC(NC=2C(=NN(C=2)C(C)(C)C#N)C)=N1 ZPPUMAMZIMPJGP-UHFFFAOYSA-N 0.000 claims description 4
- ZXIATBNUWJBBGT-JXOAFFINSA-N 5-methoxyuridine Chemical compound O=C1NC(=O)C(OC)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 ZXIATBNUWJBBGT-JXOAFFINSA-N 0.000 claims description 4
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical group CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 claims description 4
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 claims description 4
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 claims description 4
- 102000043334 C9orf72 Human genes 0.000 claims description 4
- 108700030955 C9orf72 Proteins 0.000 claims description 4
- 101150014718 C9orf72 gene Proteins 0.000 claims description 4
- 229940076606 Casein kinase 1 inhibitor Drugs 0.000 claims description 4
- 102100023677 Coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial Human genes 0.000 claims description 4
- 101710137943 Complement control protein C3 Proteins 0.000 claims description 4
- 229940126630 DNL201 Drugs 0.000 claims description 4
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 claims description 4
- 108010093031 Galactosidases Proteins 0.000 claims description 4
- 102000002464 Galactosidases Human genes 0.000 claims description 4
- 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 claims description 4
- 101000907013 Homo sapiens Coiled-coil-helix-coiled-coil-helix domain-containing protein 10, mitochondrial Proteins 0.000 claims description 4
- 101000644537 Homo sapiens Sequestosome-1 Proteins 0.000 claims description 4
- 101000891092 Homo sapiens TAR DNA-binding protein 43 Proteins 0.000 claims description 4
- 239000005536 L01XE08 - Nilotinib Substances 0.000 claims description 4
- 229940124786 LRRK2 inhibitor Drugs 0.000 claims description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 4
- 108091093037 Peptide nucleic acid Proteins 0.000 claims description 4
- 101710105644 Protein phosphatase 1A Proteins 0.000 claims description 4
- 229930185560 Pseudouridine Natural products 0.000 claims description 4
- PTJWIQPHWPFNBW-UHFFFAOYSA-N Pseudouridine C Natural products OC1C(O)C(CO)OC1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-UHFFFAOYSA-N 0.000 claims description 4
- 102000003890 RNA-binding protein FUS Human genes 0.000 claims description 4
- 108090000292 RNA-binding protein FUS Proteins 0.000 claims description 4
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 claims description 4
- 102100020814 Sequestosome-1 Human genes 0.000 claims description 4
- 102100026145 Transitional endoplasmic reticulum ATPase Human genes 0.000 claims description 4
- 101710132062 Transitional endoplasmic reticulum ATPase Proteins 0.000 claims description 4
- BLGXFZZNTVWLAY-CCZXDCJGSA-N Yohimbine Natural products C1=CC=C2C(CCN3C[C@@H]4CC[C@@H](O)[C@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-CCZXDCJGSA-N 0.000 claims description 4
- PBHFNBQPZCRWQP-AZUAARDMSA-N [(3aS,8bR)-3,4,8b-trimethyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indol-7-yl] N-phenylcarbamate Chemical compound CN([C@H]1[C@](C2=C3)(C)CCN1C)C2=CC=C3OC(=O)NC1=CC=CC=C1 PBHFNBQPZCRWQP-AZUAARDMSA-N 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- 229960003805 amantadine Drugs 0.000 claims description 4
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 4
- 239000002249 anxiolytic agent Substances 0.000 claims description 4
- 230000000949 anxiolytic effect Effects 0.000 claims description 4
- 229960004046 apomorphine Drugs 0.000 claims description 4
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 claims description 4
- 229940049706 benzodiazepine Drugs 0.000 claims description 4
- WGDUUQDYDIIBKT-UHFFFAOYSA-N beta-Pseudouridine Natural products OC1OC(CN2C=CC(=O)NC2=O)C(O)C1O WGDUUQDYDIIBKT-UHFFFAOYSA-N 0.000 claims description 4
- BLGXFZZNTVWLAY-UHFFFAOYSA-N beta-Yohimbin Natural products C1=CC=C2C(CCN3CC4CCC(O)C(C4CC33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-UHFFFAOYSA-N 0.000 claims description 4
- 210000000133 brain stem Anatomy 0.000 claims description 4
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 claims description 4
- 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 4
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 4
- 238000009223 counseling Methods 0.000 claims description 4
- CVSVTCORWBXHQV-UHFFFAOYSA-N creatine Chemical compound NC(=[NH2+])N(C)CC([O-])=O CVSVTCORWBXHQV-UHFFFAOYSA-N 0.000 claims description 4
- 229940104302 cytosine Drugs 0.000 claims description 4
- ANCLJVISBRWUTR-UHFFFAOYSA-N diaminophosphinic acid Chemical compound NP(N)(O)=O ANCLJVISBRWUTR-UHFFFAOYSA-N 0.000 claims description 4
- RJBIAAZJODIFHR-UHFFFAOYSA-N dihydroxy-imino-sulfanyl-$l^{5}-phosphane Chemical compound NP(O)(O)=S RJBIAAZJODIFHR-UHFFFAOYSA-N 0.000 claims description 4
- 229960003530 donepezil Drugs 0.000 claims description 4
- QELUYTUMUWHWMC-UHFFFAOYSA-N edaravone Chemical compound O=C1CC(C)=NN1C1=CC=CC=C1 QELUYTUMUWHWMC-UHFFFAOYSA-N 0.000 claims description 4
- 229950009041 edaravone Drugs 0.000 claims description 4
- JRURYQJSLYLRLN-BJMVGYQFSA-N entacapone Chemical compound CCN(CC)C(=O)C(\C#N)=C\C1=CC(O)=C(O)C([N+]([O-])=O)=C1 JRURYQJSLYLRLN-BJMVGYQFSA-N 0.000 claims description 4
- 229960003337 entacapone Drugs 0.000 claims description 4
- 238000002641 enzyme replacement therapy Methods 0.000 claims description 4
- 229960003980 galantamine Drugs 0.000 claims description 4
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims description 4
- 238000001415 gene therapy Methods 0.000 claims description 4
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 claims description 4
- 229960004427 isradipine Drugs 0.000 claims description 4
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 claims description 4
- 229960001848 lamotrigine Drugs 0.000 claims description 4
- 229960004502 levodopa Drugs 0.000 claims description 4
- 229960004640 memantine Drugs 0.000 claims description 4
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 claims description 4
- 230000035772 mutation Effects 0.000 claims description 4
- GECBBEABIDMGGL-RTBURBONSA-N nabilone Chemical compound C1C(=O)CC[C@H]2C(C)(C)OC3=CC(C(C)(C)CCCCCC)=CC(O)=C3[C@@H]21 GECBBEABIDMGGL-RTBURBONSA-N 0.000 claims description 4
- 229960002967 nabilone Drugs 0.000 claims description 4
- 229960002715 nicotine Drugs 0.000 claims description 4
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 4
- 235000001968 nicotinic acid Nutrition 0.000 claims description 4
- 239000011664 nicotinic acid Substances 0.000 claims description 4
- 229960003512 nicotinic acid Drugs 0.000 claims description 4
- 229960001346 nilotinib Drugs 0.000 claims description 4
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 claims description 4
- 230000000399 orthopedic effect Effects 0.000 claims description 4
- PTMHPRAIXMAOOB-UHFFFAOYSA-L phosphoramidate Chemical compound NP([O-])([O-])=O PTMHPRAIXMAOOB-UHFFFAOYSA-L 0.000 claims description 4
- 229960005095 pioglitazone Drugs 0.000 claims description 4
- DTYWJKSSUANMHD-UHFFFAOYSA-N preladenant Chemical compound C1=CC(OCCOC)=CC=C1N1CCN(CCN2C3=C(C4=NC(=NN4C(N)=N3)C=3OC=CC=3)C=N2)CC1 DTYWJKSSUANMHD-UHFFFAOYSA-N 0.000 claims description 4
- 229950008939 preladenant Drugs 0.000 claims description 4
- 229950003764 pridopidine Drugs 0.000 claims description 4
- YGKUEOZJFIXDGI-UHFFFAOYSA-N pridopidine Chemical compound C1CN(CCC)CCC1C1=CC=CC(S(C)(=O)=O)=C1 YGKUEOZJFIXDGI-UHFFFAOYSA-N 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 4
- PTJWIQPHWPFNBW-GBNDHIKLSA-N pseudouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1C1=CNC(=O)NC1=O PTJWIQPHWPFNBW-GBNDHIKLSA-N 0.000 claims description 4
- RUOKEQAAGRXIBM-GFCCVEGCSA-N rasagiline Chemical compound C1=CC=C2[C@H](NCC#C)CCC2=C1 RUOKEQAAGRXIBM-GFCCVEGCSA-N 0.000 claims description 4
- 229960000245 rasagiline Drugs 0.000 claims description 4
- 239000002342 ribonucleoside Substances 0.000 claims description 4
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 claims description 4
- 229960003946 selegiline Drugs 0.000 claims description 4
- JRPHGDYSKGJTKZ-UHFFFAOYSA-N selenophosphoric acid Chemical compound OP(O)([SeH])=O JRPHGDYSKGJTKZ-UHFFFAOYSA-N 0.000 claims description 4
- 238000011476 stem cell transplantation Methods 0.000 claims description 4
- MIQPIUSUKVNLNT-UHFFFAOYSA-N tolcapone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC(O)=C(O)C([N+]([O-])=O)=C1 MIQPIUSUKVNLNT-UHFFFAOYSA-N 0.000 claims description 4
- 229960004603 tolcapone Drugs 0.000 claims description 4
- YBZSGIWIPOUSHY-UHFFFAOYSA-N troriluzole Chemical compound NCC(=O)NCC(N(CC(NC=1SC2=C(N=1)C=CC(=C2)OC(F)(F)F)=O)C)=O YBZSGIWIPOUSHY-UHFFFAOYSA-N 0.000 claims description 4
- 229960000317 yohimbine Drugs 0.000 claims description 4
- BLGXFZZNTVWLAY-SCYLSFHTSA-N yohimbine Chemical compound C1=CC=C2C(CCN3C[C@@H]4CC[C@H](O)[C@@H]([C@H]4C[C@H]33)C(=O)OC)=C3NC2=C1 BLGXFZZNTVWLAY-SCYLSFHTSA-N 0.000 claims description 4
- AADVZSXPNRLYLV-UHFFFAOYSA-N yohimbine carboxylic acid Natural products C1=CC=C2C(CCN3CC4CCC(C(C4CC33)C(O)=O)O)=C3NC2=C1 AADVZSXPNRLYLV-UHFFFAOYSA-N 0.000 claims description 4
- 229960002911 zonisamide Drugs 0.000 claims description 4
- UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 claims description 4
- 101001109145 Homo sapiens Receptor-interacting serine/threonine-protein kinase 1 Proteins 0.000 claims description 3
- 102100022501 Receptor-interacting serine/threonine-protein kinase 1 Human genes 0.000 claims description 3
- RRTCJVBFMMTZSS-UHFFFAOYSA-N SSSSSSSSSSSSS Chemical compound SSSSSSSSSSSSS RRTCJVBFMMTZSS-UHFFFAOYSA-N 0.000 claims description 3
- OTFDPNXIVHBTKW-UHFFFAOYSA-N Tiapride hydrochloride Chemical compound [Cl-].CC[NH+](CC)CCNC(=O)C1=CC(S(C)(=O)=O)=CC=C1OC OTFDPNXIVHBTKW-UHFFFAOYSA-N 0.000 claims description 3
- HWHLPVGTWGOCJO-UHFFFAOYSA-N Trihexyphenidyl Chemical group C1CCCCC1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 HWHLPVGTWGOCJO-UHFFFAOYSA-N 0.000 claims description 3
- 229940005530 anxiolytics Drugs 0.000 claims description 3
- 230000004900 autophagic degradation Effects 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 3
- 210000001808 exosome Anatomy 0.000 claims description 3
- 210000003608 fece Anatomy 0.000 claims description 3
- 210000002751 lymph Anatomy 0.000 claims description 3
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 claims description 3
- 230000026731 phosphorylation Effects 0.000 claims description 3
- 238000006366 phosphorylation reaction Methods 0.000 claims description 3
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 claims description 3
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 claims description 3
- AKQXQLUNFKDZBN-UHFFFAOYSA-N tavapadon Chemical compound C=1C=C(C=2N(C(=O)NC(=O)C=2C)C)C(C)=CC=1OC1=NC=CC=C1C(F)(F)F AKQXQLUNFKDZBN-UHFFFAOYSA-N 0.000 claims description 3
- 229960005344 tiapride Drugs 0.000 claims description 3
- 210000001519 tissue Anatomy 0.000 claims description 3
- 230000000699 topical effect Effects 0.000 claims description 3
- 229960001032 trihexyphenidyl Drugs 0.000 claims description 3
- 210000002700 urine Anatomy 0.000 claims description 3
- NJWCVQBHNBLNOZ-ZRMYETLXSA-N (1S,3R,5R,6S,8R,10R,11S,13S,15R,16S,18R,20R,21S,23R,25R,26S,28R,30R,31S,33R,35R,36R,37R,38R,39R,40R,41R,42R,43R,44R,45R,47R,48S,49R)-5,20,30,35-tetrakis(hydroxymethyl)-49-(2-hydroxypropoxy)-10,15,25-tris(2-hydroxypropoxymethyl)-2,4,7,9,12,14,17,19,22,24,27,29,32,34-tetradecaoxaoctacyclo[31.2.2.23,6.28,11.213,16.218,21.223,26.228,31]nonatetracontane-36,37,38,39,40,41,42,43,44,45,47,48-dodecol Chemical compound CC(O)COC[C@H]1O[C@@H]2O[C@@H]3[C@@H](CO)O[C@H](O[C@@H]4[C@@H](CO)O[C@H](O[C@@H]5[C@@H](CO)O[C@H](O[C@@H]6[C@@H](COCC(C)O)O[C@H](O[C@@H]7[C@@H](CO)O[C@H](O[C@@H]8[C@@H](COCC(C)O)O[C@H](O[C@H]1C[C@H]2O)[C@H](O)[C@H]8O)[C@H](O)[C@H]7O)[C@H](O)[C@H]6O)[C@H](O)[C@H]5O)[C@H](O)[C@H]4O)[C@H](OCC(C)O)[C@H]3O NJWCVQBHNBLNOZ-ZRMYETLXSA-N 0.000 claims description 2
- PKXWXXPNHIWQHW-RCBQFDQVSA-N (2S)-2-hydroxy-3-methyl-N-[(2S)-1-[[(5S)-3-methyl-4-oxo-2,5-dihydro-1H-3-benzazepin-5-yl]amino]-1-oxopropan-2-yl]butanamide Chemical compound C1CN(C)C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](O)C(C)C)C2=CC=CC=C21 PKXWXXPNHIWQHW-RCBQFDQVSA-N 0.000 claims description 2
- YIMATHOGWXZHFX-WCTZXXKLSA-N (2r,3r,4r,5r)-5-(hydroxymethyl)-3-(2-methoxyethoxy)oxolane-2,4-diol Chemical compound COCCO[C@H]1[C@H](O)O[C@H](CO)[C@H]1O YIMATHOGWXZHFX-WCTZXXKLSA-N 0.000 claims description 2
- IVTMXOXVAHXCHI-YXLMWLKOSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid;(2s)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.NN[C@@](C(O)=O)(C)CC1=CC=C(O)C(O)=C1 IVTMXOXVAHXCHI-YXLMWLKOSA-N 0.000 claims description 2
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 claims description 2
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 claims description 2
- SGEIEGAXKLMUIZ-ZPTIMJQQSA-N (3e)-n-[(2r)-2-hydroxy-3-piperidin-1-ylpropoxy]-1-oxidopyridin-1-ium-3-carboximidoyl chloride Chemical compound C([C@H](O)CN1CCCCC1)O\N=C(\Cl)C1=CC=C[N+]([O-])=C1 SGEIEGAXKLMUIZ-ZPTIMJQQSA-N 0.000 claims description 2
- RLUCYBFCLXANSO-BTJKTKAUSA-N 1-[3-[2-(1-benzothiophen-5-yl)ethoxy]propyl]azetidin-3-ol;(z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.C1C(O)CN1CCCOCCC1=CC=C(SC=C2)C2=C1 RLUCYBFCLXANSO-BTJKTKAUSA-N 0.000 claims description 2
- YFRBKEVUUCQYOW-UHFFFAOYSA-N 1-[6-[(3-cyclobutyl-1,2,4,5-tetrahydro-3-benzazepin-7-yl)oxy]pyridin-3-yl]pyrrolidin-2-one Chemical compound O=C1CCCN1C(C=N1)=CC=C1OC1=CC=C(CCN(CC2)C3CCC3)C2=C1 YFRBKEVUUCQYOW-UHFFFAOYSA-N 0.000 claims description 2
- JSAQBOQCZJHWMA-XMMPIXPASA-N 1-tert-butyl-N-[(5R)-8-[2-[(1-methylpyrazol-4-yl)amino]pyrimidin-4-yl]-2-(oxetan-3-yl)-1,3,4,5-tetrahydro-2-benzazepin-5-yl]triazole-4-carboxamide Chemical compound C(C)(C)(C)N1N=NC(=C1)C(=O)N[C@H]1C2=C(CN(CC1)C1COC1)C=C(C=C2)C1=NC(=NC=C1)NC=1C=NN(C=1)C JSAQBOQCZJHWMA-XMMPIXPASA-N 0.000 claims description 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 2
- JJZFWROHYSMCMU-UHFFFAOYSA-N 3-(benzenesulfonyl)-8-piperazin-1-ylquinoline Chemical compound C=1N=C2C(N3CCNCC3)=CC=CC2=CC=1S(=O)(=O)C1=CC=CC=C1 JJZFWROHYSMCMU-UHFFFAOYSA-N 0.000 claims description 2
- LDCYZAJDBXYCGN-UHFFFAOYSA-N 5-hydroxytryptophan Chemical compound C1=C(O)C=C2C(CC(N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-UHFFFAOYSA-N 0.000 claims description 2
- FUZYTVDVLBBXDL-UHFFFAOYSA-N 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide Chemical compound N1C2=CC=C(Cl)C=C2C2=C1C(C(=O)N)CCC2 FUZYTVDVLBBXDL-UHFFFAOYSA-N 0.000 claims description 2
- IHLOTZVBEUFDMD-UUOKFMHZSA-N 7-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-2,2-dioxo-1h-imidazo[4,5-c][1,2,6]thiadiazin-4-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(NS(=O)(=O)NC2=O)=C2N=C1 IHLOTZVBEUFDMD-UUOKFMHZSA-N 0.000 claims description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
- 108020000948 Antisense Oligonucleotides Proteins 0.000 claims description 2
- 229940125889 BIIB091 Drugs 0.000 claims description 2
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 claims description 2
- XXGMIHXASFDFSM-UHFFFAOYSA-N Delta9-tetrahydrocannabinol Natural products CCCCCc1cc2OC(C)(C)C3CCC(=CC3c2c(O)c1O)C XXGMIHXASFDFSM-UHFFFAOYSA-N 0.000 claims description 2
- 102000003951 Erythropoietin Human genes 0.000 claims description 2
- 108090000394 Erythropoietin Proteins 0.000 claims description 2
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 claims description 2
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 claims description 2
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 claims description 2
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 claims description 2
- 102100029199 Iduronate 2-sulfatase Human genes 0.000 claims description 2
- 229940125966 JNJ-54861911 Drugs 0.000 claims description 2
- 108010006746 KCNQ2 Potassium Channel Proteins 0.000 claims description 2
- 108010038888 KCNQ3 Potassium Channel Proteins 0.000 claims description 2
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 claims description 2
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 claims description 2
- JLEBZPBDRKPWTD-TURQNECASA-O N-ribosylnicotinamide Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](CO)O2)O)=C1 JLEBZPBDRKPWTD-TURQNECASA-O 0.000 claims description 2
- 241001272996 Polyphylla fullo Species 0.000 claims description 2
- 102100034354 Potassium voltage-gated channel subfamily KQT member 2 Human genes 0.000 claims description 2
- 102100034360 Potassium voltage-gated channel subfamily KQT member 3 Human genes 0.000 claims description 2
- QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 claims description 2
- 229940126644 SAGE-718 Drugs 0.000 claims description 2
- LKJCZXIGFPOQPC-UHFFFAOYSA-N SSSSSSSSSSSSSSSS Chemical compound SSSSSSSSSSSSSSSS LKJCZXIGFPOQPC-UHFFFAOYSA-N 0.000 claims description 2
- VDTZYABQBPMANF-UHFFFAOYSA-N SSSSSSSSSSSSSSSSSSS Chemical compound SSSSSSSSSSSSSSSSSSS VDTZYABQBPMANF-UHFFFAOYSA-N 0.000 claims description 2
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 claims description 2
- QHMBSVQNZZTUGM-UHFFFAOYSA-N Trans-Cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-UHFFFAOYSA-N 0.000 claims description 2
- LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 claims description 2
- 229940123445 Tricyclic antidepressant Drugs 0.000 claims description 2
- VEPKQEUBKLEPRA-UHFFFAOYSA-N VX-745 Chemical compound FC1=CC(F)=CC=C1SC1=NN2C=NC(=O)C(C=3C(=CC=CC=3Cl)Cl)=C2C=C1 VEPKQEUBKLEPRA-UHFFFAOYSA-N 0.000 claims description 2
- YFHRCLAKZBDRHN-MRXNPFEDSA-N [(3s)-1-azabicyclo[2.2.2]octan-3-yl] n-[2-[2-(4-fluorophenyl)-1,3-thiazol-4-yl]propan-2-yl]carbamate Chemical compound O([C@H]1C2CCN(CC2)C1)C(=O)NC(C)(C)C(N=1)=CSC=1C1=CC=C(F)C=C1 YFHRCLAKZBDRHN-MRXNPFEDSA-N 0.000 claims description 2
- 229960004308 acetylcysteine Drugs 0.000 claims description 2
- 229960005339 acitretin Drugs 0.000 claims description 2
- 229960002964 adalimumab Drugs 0.000 claims description 2
- 238000011374 additional therapy Methods 0.000 claims description 2
- 229950008995 aducanumab Drugs 0.000 claims description 2
- MMLDHJRGTZHNHV-BPGUCPLFSA-N alicapistat Chemical compound O=C([C@@H]1N(C(=O)CC1)CC=1C=CC=CC=1)NC(C(=O)C(=O)NC1CC1)CC1=CC=CC=C1 MMLDHJRGTZHNHV-BPGUCPLFSA-N 0.000 claims description 2
- IHUNBGSDBOWDMA-AQFIFDHZSA-N all-trans-acitretin Chemical compound COC1=CC(C)=C(\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O)C(C)=C1C IHUNBGSDBOWDMA-AQFIFDHZSA-N 0.000 claims description 2
- 230000000735 allogeneic effect Effects 0.000 claims description 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 2
- 239000003146 anticoagulant agent Substances 0.000 claims description 2
- 229940127219 anticoagulant drug Drugs 0.000 claims description 2
- 239000000935 antidepressant agent Substances 0.000 claims description 2
- 229940005513 antidepressants Drugs 0.000 claims description 2
- 239000000427 antigen Substances 0.000 claims description 2
- 102000036639 antigens Human genes 0.000 claims description 2
- 108091007433 antigens Proteins 0.000 claims description 2
- 239000000164 antipsychotic agent Substances 0.000 claims description 2
- 229940005529 antipsychotics Drugs 0.000 claims description 2
- 229940039856 aricept Drugs 0.000 claims description 2
- 229950011582 arimoclomol Drugs 0.000 claims description 2
- 239000000607 artificial tear Substances 0.000 claims description 2
- VLLFGVHGKLDDLW-SFHVURJKSA-N atabecestat Chemical compound C=1C(NC(=O)C=2N=CC(=CC=2)C#N)=CC=C(F)C=1[C@]1(C)C=CSC(N)=N1 VLLFGVHGKLDDLW-SFHVURJKSA-N 0.000 claims description 2
- 229960002170 azathioprine Drugs 0.000 claims description 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims description 2
- JUTBAVRYDAKVGQ-UHFFFAOYSA-N bdth2 Chemical compound SCCNC(=O)C1=CC=CC(C(=O)NCCS)=C1 JUTBAVRYDAKVGQ-UHFFFAOYSA-N 0.000 claims description 2
- 150000001557 benzodiazepines Chemical class 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- 229950003210 bradanicline Drugs 0.000 claims description 2
- OXKRFEWMSWPKKV-RXVVDRJESA-N bradanicline Chemical compound C([C@@H]1N2CCC(CC2)[C@@H]1NC(=O)C=1OC2=CC=CC=C2C=1)C1=CC=CN=C1 OXKRFEWMSWPKKV-RXVVDRJESA-N 0.000 claims description 2
- QHMBSVQNZZTUGM-ZWKOTPCHSA-N cannabidiol Chemical compound OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-ZWKOTPCHSA-N 0.000 claims description 2
- 229950011318 cannabidiol Drugs 0.000 claims description 2
- ZTGXAWYVTLUPDT-UHFFFAOYSA-N cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CC=C(C)C1 ZTGXAWYVTLUPDT-UHFFFAOYSA-N 0.000 claims description 2
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 claims description 2
- 229960000623 carbamazepine Drugs 0.000 claims description 2
- 229940047495 celebrex Drugs 0.000 claims description 2
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 2
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 claims description 2
- 229960001076 chlorpromazine Drugs 0.000 claims description 2
- 235000012000 cholesterol Nutrition 0.000 claims description 2
- 239000000544 cholinesterase inhibitor Substances 0.000 claims description 2
- 229960003405 ciprofloxacin Drugs 0.000 claims description 2
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 claims description 2
- 229960003120 clonazepam Drugs 0.000 claims description 2
- 229960001338 colchicine Drugs 0.000 claims description 2
- 201000008692 congenital stationary night blindness 1A Diseases 0.000 claims description 2
- 239000003246 corticosteroid Substances 0.000 claims description 2
- 229960001334 corticosteroids Drugs 0.000 claims description 2
- 229960003624 creatine Drugs 0.000 claims description 2
- 239000006046 creatine Substances 0.000 claims description 2
- 229960003834 dapagliflozin Drugs 0.000 claims description 2
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 claims description 2
- 229960001985 dextromethorphan Drugs 0.000 claims description 2
- 229960003529 diazepam Drugs 0.000 claims description 2
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 2
- PCXRACLQFPRCBB-ZWKOTPCHSA-N dihydrocannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)C)CCC(C)=C1 PCXRACLQFPRCBB-ZWKOTPCHSA-N 0.000 claims description 2
- 229940052760 dopamine agonists Drugs 0.000 claims description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 claims description 2
- 230000009977 dual effect Effects 0.000 claims description 2
- 229940105423 erythropoietin Drugs 0.000 claims description 2
- WRUIDZKNUAHKTR-UHFFFAOYSA-N ethyl 5-(benzylamino)-6-(cyclohexylamino)pyridine-3-carboxylate Chemical compound C=1C=CC=CC=1CNC1=CC(C(=O)OCC)=CN=C1NC1CCCCC1 WRUIDZKNUAHKTR-UHFFFAOYSA-N 0.000 claims description 2
- 229940108366 exelon Drugs 0.000 claims description 2
- 229960002297 fenofibrate Drugs 0.000 claims description 2
- 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 claims description 2
- 229960002870 gabapentin Drugs 0.000 claims description 2
- 238000001476 gene delivery Methods 0.000 claims description 2
- 230000002068 genetic effect Effects 0.000 claims description 2
- 229960004580 glibenclamide Drugs 0.000 claims description 2
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 claims description 2
- 229960003878 haloperidol Drugs 0.000 claims description 2
- 235000004280 healthy diet Nutrition 0.000 claims description 2
- 239000003395 histamine H3 receptor antagonist Substances 0.000 claims description 2
- 238000002639 hyperbaric oxygen therapy Methods 0.000 claims description 2
- 229960002396 idursulfase Drugs 0.000 claims description 2
- 108010072166 idursulfase Proteins 0.000 claims description 2
- 239000003018 immunosuppressive agent Substances 0.000 claims description 2
- 230000005764 inhibitory process Effects 0.000 claims description 2
- JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 claims description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-M lipoate Chemical compound [O-]C(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-M 0.000 claims description 2
- 235000019136 lipoic acid Nutrition 0.000 claims description 2
- FRQMUZJSZHZSGN-HBNHAYAOSA-N medroxyprogesterone Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FRQMUZJSZHZSGN-HBNHAYAOSA-N 0.000 claims description 2
- 229960004616 medroxyprogesterone Drugs 0.000 claims description 2
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 claims description 2
- 229960004023 minocycline Drugs 0.000 claims description 2
- 239000003158 myorelaxant agent Substances 0.000 claims description 2
- 229940069817 neflamapimod Drugs 0.000 claims description 2
- 230000001537 neural effect Effects 0.000 claims description 2
- 239000002581 neurotoxin Substances 0.000 claims description 2
- 231100000618 neurotoxin Toxicity 0.000 claims description 2
- 235000020956 nicotinamide riboside Nutrition 0.000 claims description 2
- 239000011618 nicotinamide riboside Substances 0.000 claims description 2
- 235000016709 nutrition Nutrition 0.000 claims description 2
- 229960005017 olanzapine Drugs 0.000 claims description 2
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 claims description 2
- 229940005483 opioid analgesics Drugs 0.000 claims description 2
- RKEWSXXUOLRFBX-UHFFFAOYSA-N pimavanserin Chemical compound C1=CC(OCC(C)C)=CC=C1CNC(=O)N(C1CCN(C)CC1)CC1=CC=C(F)C=C1 RKEWSXXUOLRFBX-UHFFFAOYSA-N 0.000 claims description 2
- 229960003300 pimavanserin Drugs 0.000 claims description 2
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 2
- 229960001233 pregabalin Drugs 0.000 claims description 2
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 claims description 2
- 239000003368 psychostimulant agent Substances 0.000 claims description 2
- 229960004431 quetiapine Drugs 0.000 claims description 2
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 claims description 2
- 229940051845 razadyne Drugs 0.000 claims description 2
- 238000009252 recreational therapy Methods 0.000 claims description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 claims description 2
- 229940016667 resveratrol Drugs 0.000 claims description 2
- 235000021283 resveratrol Nutrition 0.000 claims description 2
- 229960004181 riluzole Drugs 0.000 claims description 2
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 claims description 2
- 229960001534 risperidone Drugs 0.000 claims description 2
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 claims description 2
- 238000009168 stem cell therapy Methods 0.000 claims description 2
- 238000009580 stem-cell therapy Methods 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims description 2
- 238000011477 surgical intervention Methods 0.000 claims description 2
- 238000001356 surgical procedure Methods 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 claims description 2
- 230000008685 targeting Effects 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- 229960005333 tetrabenazine Drugs 0.000 claims description 2
- 229960002663 thioctic acid Drugs 0.000 claims description 2
- PMJIHLSCWIDGMD-UHFFFAOYSA-N tideglusib Chemical compound O=C1SN(C=2C3=CC=CC=C3C=CC=2)C(=O)N1CC1=CC=CC=C1 PMJIHLSCWIDGMD-UHFFFAOYSA-N 0.000 claims description 2
- 229950005284 tideglusib Drugs 0.000 claims description 2
- 238000007483 tonsillectomy Methods 0.000 claims description 2
- 239000003029 tricyclic antidepressant agent Substances 0.000 claims description 2
- 229940121629 troriluzole Drugs 0.000 claims description 2
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 claims description 2
- 229960001661 ursodiol Drugs 0.000 claims description 2
- 229940102566 valproate Drugs 0.000 claims description 2
- 229940121352 zilucoplan Drugs 0.000 claims description 2
- 229960001475 zolpidem Drugs 0.000 claims description 2
- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 8
- 206010006074 Brachial plexus injury Diseases 0.000 claims 3
- 230000007850 degeneration Effects 0.000 claims 2
- 230000002183 duodenal effect Effects 0.000 claims 2
- BVBRUQYHUXKZMQ-JNVAYQLDSA-N (3s,8s,9s,10r,13r,14s,17r)-3,10,13-trimethyl-17-[(2r,5s)-6,6,6-trifluoro-5-hydroxy-5-methylhexan-2-yl]-1,2,4,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-ol Chemical compound C1C=C2C[C@@](C)(O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@@H](CC[C@](C)(O)C(F)(F)F)C)[C@@]1(C)CC2 BVBRUQYHUXKZMQ-JNVAYQLDSA-N 0.000 claims 1
- 241000321096 Adenoides Species 0.000 claims 1
- 229920002683 Glycosaminoglycan Polymers 0.000 claims 1
- WXNXCEHXYPACJF-ZETCQYMHSA-M N-acetyl-L-leucinate Chemical compound CC(C)C[C@@H](C([O-])=O)NC(C)=O WXNXCEHXYPACJF-ZETCQYMHSA-M 0.000 claims 1
- 208000014060 Niemann-Pick disease Diseases 0.000 claims 1
- 210000002534 adenoid Anatomy 0.000 claims 1
- 210000004227 basal ganglia Anatomy 0.000 claims 1
- 150000005690 diesters Chemical class 0.000 claims 1
- 210000000609 ganglia Anatomy 0.000 claims 1
- 229960003444 immunosuppressant agent Drugs 0.000 claims 1
- 201000007769 mucolipidosis Diseases 0.000 claims 1
- 229960002748 norepinephrine Drugs 0.000 claims 1
- 238000002271 resection Methods 0.000 claims 1
- 239000003751 serotonin 6 antagonist Substances 0.000 claims 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 claims 1
- 229940125706 skeletal muscle relaxant agent Drugs 0.000 claims 1
- 239000000021 stimulant Substances 0.000 claims 1
- 208000027418 Wounds and injury Diseases 0.000 description 5
- 230000006378 damage Effects 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 210000005036 nerve Anatomy 0.000 description 5
- ZBQPJUMVWHDCRQ-UHFFFAOYSA-N SSSSSSSSSSSSSS Chemical compound SSSSSSSSSSSSSS ZBQPJUMVWHDCRQ-UHFFFAOYSA-N 0.000 description 2
- 230000001773 anti-convulsant effect Effects 0.000 description 2
- 229960003965 antiepileptics Drugs 0.000 description 2
- VIYKYVYAKVNDPS-HKGPVOKGSA-N (2s)-2-azanyl-3-[3,4-bis(oxidanyl)phenyl]propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1.OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 VIYKYVYAKVNDPS-HKGPVOKGSA-N 0.000 description 1
- 108091005435 5-HT6 receptors Proteins 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- WDZRUXKVLXELHY-UHFFFAOYSA-N SSSSSSSSSSSSSSSSSS Chemical compound SSSSSSSSSSSSSSSSSS WDZRUXKVLXELHY-UHFFFAOYSA-N 0.000 description 1
- 229940121991 Serotonin and norepinephrine reuptake inhibitor Drugs 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000003775 serotonin noradrenalin reuptake inhibitor Substances 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962864988P | 2019-06-21 | 2019-06-21 | |
| US62/864,988 | 2019-06-21 | ||
| US201962871356P | 2019-07-08 | 2019-07-08 | |
| US62/871,356 | 2019-07-08 | ||
| PCT/US2020/038703 WO2020257631A2 (en) | 2019-06-21 | 2020-06-19 | Ppm1a inhibitors and methods of using same |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2022537581A JP2022537581A (ja) | 2022-08-26 |
| JP2022537581A5 JP2022537581A5 (https=) | 2023-06-26 |
| JPWO2020257631A5 true JPWO2020257631A5 (https=) | 2023-06-26 |
Family
ID=74040507
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021576065A Withdrawn JP2022537581A (ja) | 2019-06-21 | 2020-06-19 | Ｐｐｍ１阻害剤およびその使用方法 |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US20220372489A1 (https=) |
| EP (1) | EP3987030A4 (https=) |
| JP (1) | JP2022537581A (https=) |
| KR (1) | KR20220035137A (https=) |
| CN (1) | CN114729355A (https=) |
| AU (1) | AU2020296104A1 (https=) |
| CA (1) | CA3144063A1 (https=) |
| IL (1) | IL289127A (https=) |
| WO (1) | WO2020257631A2 (https=) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP4392562A4 (en) * | 2021-08-27 | 2025-09-24 | Ionis Pharmaceuticals Inc | COMPOUNDS AND METHODS FOR MODULATING SCN1A EXPRESSION |
| WO2023102188A1 (en) * | 2021-12-03 | 2023-06-08 | Quralis Corporation | Gapmer antisense oligonucleotides with modified backbone chemistries |
| KR102856378B1 (ko) * | 2022-09-30 | 2025-09-08 | 주식회사 젬백스앤카엘 | 4r 타우병증의 치료 또는 예방용 펩티드 |
| KR102775989B1 (ko) * | 2022-11-01 | 2025-03-04 | 윤주호 | 콜치신과 메트포르민을 유효성분으로 하는 퇴행성 신경계 질환의 예방 또는 치료용 조성물 |
| CN117031014A (zh) * | 2023-08-14 | 2023-11-10 | 陕西脉元生物科技有限公司 | 抗matr3自身抗体的试剂在制备检测神经系统自身免疫疾病的产品中的应用及试剂盒 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2227306A1 (en) * | 1995-09-01 | 1997-03-27 | Ramot-University Authority For Applied Research And Industrial Developme Nt Ltd. | Manipulation and detection of protein phosphatase 2c - pp2c.alpha. - expression in tumor cells for cancer therapy, prevention and detection |
| JPH11512294A (ja) * | 1995-09-01 | 1999-10-26 | ラモット ユニヴァーシティー オーソリティ フォア アップライド リサーチ アンド インダストリアル ディヴェロプメント リミテッド | 癌の治療、予防および発見を目的とする腫瘍細胞での蛋白ホスファターゼ２Ｃ−ＰＰ２Ｃα−発現の操作と検出 |
| US20030050270A1 (en) * | 1998-11-20 | 2003-03-13 | Monia Brett P. | Antisense modulation of Inhibitor-kappa B Kinase-beta expression |
| WO2003014321A2 (en) * | 2001-08-10 | 2003-02-20 | The Rockefeller University | Compositions and methods for modulation of darpp-32 phosphorylation |
| GB0207251D0 (en) * | 2002-03-27 | 2002-05-08 | Isis Innovation | Lymphoma-associated antigens |
| US20040102397A1 (en) * | 2002-11-22 | 2004-05-27 | Isis Pharmaceuticals Inc. | Modulation of PPM1B expression |
| AU2003270900A1 (en) * | 2002-09-25 | 2004-04-19 | Pharmacia Corporation | Antisense modulation of microsomal prostaglandin e2 synthase expression |
| AU2003271651A1 (en) * | 2002-10-04 | 2004-04-23 | Bayer Healthcare Ag | Regulation of human pp2c-like protein phosphatase |
| WO2011073903A1 (en) * | 2009-12-14 | 2011-06-23 | Koninklijke Philips Electronics N.V. | Novel tumor markers |
| US20140200261A1 (en) * | 2013-01-17 | 2014-07-17 | Moderna Therapeutics, Inc. | Signal-sensor polynucleotides for the alteration of cellular phenotypes |
| US11096956B2 (en) * | 2015-12-14 | 2021-08-24 | Stoke Therapeutics, Inc. | Antisense oligomers and uses thereof |
-
2020
- 2020-06-19 US US17/621,320 patent/US20220372489A1/en active Pending
- 2020-06-19 CN CN202080057853.2A patent/CN114729355A/zh active Pending
- 2020-06-19 EP EP20825513.3A patent/EP3987030A4/en not_active Withdrawn
- 2020-06-19 CA CA3144063A patent/CA3144063A1/en active Pending
- 2020-06-19 WO PCT/US2020/038703 patent/WO2020257631A2/en not_active Ceased
- 2020-06-19 JP JP2021576065A patent/JP2022537581A/ja not_active Withdrawn
- 2020-06-19 KR KR1020227002134A patent/KR20220035137A/ko not_active Withdrawn
- 2020-06-19 AU AU2020296104A patent/AU2020296104A1/en not_active Abandoned
-
2021
- 2021-12-19 IL IL289127A patent/IL289127A/en unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20160201064A1 (en) | Compositions and methods for modulating expression of frataxin | |
| TW202020154A (zh) | 用於減少atxn2表現之化合物及方法 | |
| JP2019529489A (ja) | タウ発現を低減するための化合物及び方法 | |
| CA3142526A1 (en) | Oligonucleotides and methods of use for treating neurological diseases | |
| JP2022537581A (ja) | Ｐｐｍ１阻害剤およびその使用方法 | |
| TW201923082A (zh) | 用於降低snca表現之化合物及方法 | |
| EP3765476B1 (en) | Modified oligonucleotides for use in treatment of tauopathies | |
| JP2021535204A5 (https=) | ||
| AU2022400851A1 (en) | Treatment of neurological diseases using modulators of unc13a gene transcripts | |
| TW202328447A (zh) | 用於降低dmpk表現之化合物與方法 | |
| JPWO2020257631A5 (https=) | ||
| JPWO2020247419A5 (https=) | ||
| TW202111123A (zh) | 用於減少fus 表現之化合物及方法 | |
| JP7788561B2 (ja) | アンチセンスオリゴヌクレオチド及びその使用 | |
| CN120118142A (zh) | 用于调节血管紧张素原表达的化合物和方法 | |
| JP2023528435A (ja) | 遺伝子転写物のモジュレーターを使用する神経学的疾患の処置 | |
| JP2026506514A (ja) | Ｓｙｆ２アンチセンスオリゴヌクレオチド | |
| CN119452086A (zh) | 具有修饰的主链化学的gapmer反义寡核苷酸 | |
| JP2025514346A (ja) | Ｓｙｆ２アンチセンスオリゴヌクレオチド | |
| WO2023102548A1 (en) | Treatment of neurological diseases using modulators of kcnq2 gene transcripts | |
| HK40121931A (zh) | 具有修饰的主链化学的gapmer反义寡核苷酸 | |
| JPWO2023102188A5 (https=) | ||
| EA053024B1 (ru) | Антисмысловые олигонуклеотиды-переключатели сплайсинга с модифицированной химией скелета | |
| WO2024249791A2 (en) | Modified unc13a oligonucleotides | |
| HK40097883A (zh) | 使用基因转录物调控剂治疗神经学疾病 |