发明名称 MGMT inhibitor combination for the treatment of neoplastic disorders
摘要 A method of treating a neoplastic disease in a subject includes administering to neoplastic cells of the subject an MGMT inhibitor and at least one of an antimitotic agent or a DNA damaging agent.
申请公布号 US8791081(B2) 申请公布日期 2014.07.29
申请号 US200812529643 申请日期 2008.02.29
申请人 Case Western Reserve University 发明人 Liu Lili;Gerson Stanton
分类号 A61K31/70;A61K31/708;A61K31/7064;A61K31/7068;A61K31/337;A61K31/335;A61K31/522;A61K31/505;A61P35/00 主分类号 A61K31/70
代理机构 Tarolli, Sundheim Covell & Tummino LLP 代理人 Tarolli, Sundheim Covell & Tummino LLP
主权项 1. A method of treating a cancer in a subject that is resistant to treatment with an antimitotic agent comprising: administering to the cancer of the subject an MGMT inhibitor and an antimitotic agent; the MGMT inhibitor being administered at an amount effective to potentiate the effect of the antimitotic agent at promoting mitotic cell death of the cancer, wherein the antimitotic agent is a taxane and the MGMT inhibitor is selected from the group consisting of O6-benzylguanine (BG), O6-2-fluoropyridinylmethyl guanine (FPG), O6-3-iodobenzyl guanine, O6-4-bromophenylguanine (PaTrin-2, UK), and O6-5-iodothenylguanine, O6-benzyl-8-oxoguanine (MW 257), O6-(p-chlorobenzyl)guanine, O6-(p-methylbenzyl)guanine (MW255), O6-(p-bromobenzyl)guanine (MW 320), O6-(p-isopropylbenzyl)guanine (MW 283), O6-(3,5-dimethylbenzyl)guanine (MW 269), O6-(p-n-butylbenzyl)guanine (MW 297), O6-(p-hydroxymethybenzyl)guanine (MW271), O6-benzylhypoxanthine, N2-acetyl-O6-benzylguanine (MW 283), N2-acetyl-O6-benzyl-8-oxoguanine (MW 299), 2-amino-6-(p-methyl-benzyl-thio)purine, 2-amino-6-(benzyloxy)-9-[(ethoxycarbonyl)methyl]purine, 2-amino-6-(benzyloxy)-9-(pivaloyloxymethyl)purine, 2-amino-6-(benzyl-thio)purine, O6-benzyl-7,8-dihydro-8-oxoguanine (8-oxo-BG), 2,4,5-triamino-6-benzyloxyprimidine (5-amino-BP), O6-benzyl-9-[(3-oxo-5α-androstan-17β-yloxycarbonyl)methyl]guanine (DHT-BG), O6-benzyl-9-[(3-oxo-4-androsten-17β-yloxycarbonyl)methyl(guanine (AND-BG), 8-amino-O6-benzylguanine (8-amino-BG), C8-linker-glucose-conjugates thereof, 2,4-diamino-6 benzyloxy-5-nitrosopyrimidine (5-nitroso-BP) and 2,4-diamino-6-benzyloxy-5-nitropyrimidine (5-nitro-BP), 2-amino-4-benzyloxy-5-nitropyrimidine, and combinations thereof.
地址 Cleveland OH US