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US 12,453,733 B2Granted
Composition for prevention or treatment of intractable epilepsy comprising mTOR inhibitor
AssigneeSoVarGen Co., Ltd.
InventorsJeong Ho Lee, Jae Seok Lim, Woo-Il Kim, Dong Seok Kim, Hoon Chul Kang, Se Hoon Kim
Life of this patent
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Abstract
Provided is a use of the prophylaxis, amelioration or therapy of intractable epilepsy, for example, Focal Cortical Dysplasia (FCD).
Claims11
A method for treating Focal Cortical Dysplasia (FCD) type II in a subject, comprising administering to the subject an effective amount of an mTOR inhibitor, wherein the subject has a brain somatic mutation in mTOR, TSC1, TSC2, AKT3, or PIK3CA,
- wherein the mTOR inhibitor is Rapamycin, 3-[2,4-bis[(3S)-3methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-N-methylbenzamide (AZD2014), 2methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1yl)phenyl]propanenitrile (BEZ235), (Z)-but-2-enedioic acid;
- 8-(6-methoxypyridin-3-yl)-3methyl-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]imidazo [4,5-c]quinolin-2-one (BGT226), Everolimus, 5-ethyl-3-[2-methyl-6-(1H-1,2,4-triazol-5-yl)pyridin-3yl]-7,8-dihydropyrazino[2,3-b]pyrazin-6-one (CC-115), 3-[6-(2-hydroxypropan-2 yl)pyridin-3-yl]-5-(4-methoxycyclohexyl)-7,8-dihydropyrazino[2,3-b]pyrazin-6-one (CC223), 8-[5-(2-hydroxypropan-2-yl)pyridin-3-yl]-1-[(2S)-2-methoxypropyl]-3methylimidazo[4,5-c]quinolin-2-one (LY3023414), P7170, 1-{(2R)-4-[2-(2Aminopyrimidin-5-yl)-6-(morpholin-4-yl)-9-(2,2,2-trifluoroethyl)-9H-purin-8-yl]-2 methylpiperazin-1-yl}ethan-1-one (DS-7423), (4-[(5Z)-4-amino-5-(7-methoxyindol-2 ylidene)-1H-imidazo[5,1-f][|1,2,4]triazin-7-yl]cyclohexane-1-carboxylic acid) (OSI-027), 2-amino-8-[4-(2-hydroxyethoxy)cyclohexyl]-6-(6-methoxypyridin-3-yl)-4methylpyrido[2,3-d]pyrimidin-7-one (PF-04691502), 1-[4-[4-(dimethylamino)piperidine-1carbonyl]phenyl]-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea (PF-05212384), Temsirolimus, [6-(2-amino-1,3-benzoxazol-5-yl)imidazo [1,2-a]pyridin-3-yl]morpholin-4-ylmethanone (MLN1117), Ridaforolimus, Metformin, N-[4-[[3-(3,5dimethoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl]-3-methoxy-4-methylbenzamide (XL765), 2-amino-8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7-one (SAR245409), (3S)-4-[[(1S)-1-carboxy-2-hydroxyethyl]amino]-3-[2-[[(2S)-5(diaminomethylideneamino)-2-[[4-oxo-4-[[4-(4-oxo-8-phenylchromen-2-yl)morpholin-4 ium-4-yl]methoxy]butanoyl]amino]pentanoyl]amino]acetyl]amino]-4-oxobutanoate (SF1126), 5-(8-methyl-2-morpholin-4-yl-9-propan-2-ylpurin-6-yl)pyrimidin-2-amine (VS5584), (2S)-1-[4-[[2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholin-4-ylthieno[3,2d]pyrimidin-6-yl]methyl]piperazin-1-yl]-2-hydroxypropan-1-one (GDC0980), or a compound of any of chemical formulae 1 to 5:
- or a pharmaceutically-acceptable salt thereof.
A method for treating Focal Cortical Dysplasia (FCD) type II in a subject, the method comprising reducing phosphorylation of S6K by administering an mTOR inhibitor, wherein the subject has a brain somatic mutation in mTOR, TSC1, TSC2, AKT3, or PIK3CA,
- wherein the mTOR inhibitor is Rapamycin, 3-[2,4-bis[(3S)-3methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-N-methylbenzamide (AZD2014), 2methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1yl)phenyl]propanenitrile (BEZ235), (Z)-but-2-enedioic acid;
- 8-(6-methoxypyridin-3-yl)-3methyl-1-[4-piperazin-1-yl-3-(trifluoromethyl)phenyl]imidazo[4,5-c]quinolin-2-one (BGT226), Everolimus, 5-ethyl-3-[2-methyl-6-(1H-1,2,4-triazol-5-yl)pyridin-3yl]-7,8-dihydropyrazino[2,3-b]pyrazin-6-one (CC-115), 3-[6-(2-hydroxypropan-2 yl)pyridin-3-yl]-5-(4-methoxycyclohexyl)-7,8-dihydropyrazino[2,3-b]pyrazin-6-one (CC223), 8-[5-(2-hydroxypropan-2-yl)pyridin-3-yl]-1-[(2S)-2-methoxypropyl]-3methylimidazo[4,5-c]quinolin-2-one (LY3023414), P7170, 1-{(2R)-4-[2-(2Aminopyrimidin-5-yl)-6-(morpholin-4-yl)-9-(2,2,2-trifluoroethyl)-9H-purin-8-yl]-2 methylpiperazin-1-yl}ethan-1-one (DS-7423), (4-[(5Z)-4-amino-5-(7-methoxyindol-2 ylidene)-1H-imidazo[5,1-f][1,2,4]triazin-7-yl]cyclohexane-1-carboxylic acid) (OSI-027), 2-amino-8-[4-(2-hydroxyethoxy) cyclohexyl]-6-(6-methoxypyridin-3-yl)-4methylpyrido[2,3-d]pyrimidin-7-one (PF-04691502), 1-[4-[4-(dimethylamino)piperidine-1carbonyl]phenyl]-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea (PF-05212384), Temsirolimus, [6-(2-amino-1,3-benzoxazol-5-yl)imidazo[1,2-a]pyridin-3-yl]morpholin-4-ylmethanone (MLN1117), Ridaforolimus, Metformin, N-[4-[[3-(3,5dimethoxyanilino) quinoxalin-2-yl]sulfamoyl]phenyl]-3-methoxy-4-methylbenzamide (XL765), 2-amino-8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)pyrido[2,3-d]pyrimidin-7-one (SAR245409), (3S)-4-[[(1S)-1-carboxy-2-hydroxyethyl]amino]-3-(2S)-5(diaminomethylideneamino)-2-[[4-oxo-4-[[4-(4-oxo-8-phenylchromen-2-yl) morpholin-4 ium-4-yl]methoxy]butanoyl]amino]pentanoyl]amino]acetyl]amino]-4-oxobutanoate (SF1126), 5-(8-methyl-2-morpholin-4-yl-9-propan-2-ylpurin-6-yl)pyrimidin-2-amine (VS5584), (2S)-1-[4-[[2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholin-4-ylthieno[3,2d]pyrimidin-6-yl]methyl]piperazin-1-yl]-2-hydroxypropan-1-one (GDC0980), or a compound of any of chemical formulae 1 to 5:
- or a pharmaceutically-acceptable salt thereof.
Dependencies are inferred from the claim text.