Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin
Discovery of GSK2126458, a Highly Potent Inhibitor of PI3K and the Mammalian Target of Rapamycin
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DOI：
10.1021/ml900028r
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发表时间：
2010-04-01
影响因子：
4.2
通讯作者：
Dhanak, Dashyant
中科院分区：
文献类型：
--
作者：
Knight, Steven D.;Adams, Nicholas D.;Dhanak, Dashyant
磷脂酰肌醇3-激酶α雷帕霉素（mTOR）是一种IV类PI 3 K蛋白激酶，也是细胞生长的中心调节因子，并且mTOR抑制剂被认为增强PI 3 K/AKT途径抑制2的抗增殖功效，4-二氟-N-{2-（甲基氧基）-5-[4-（4-哒嗪基）-6-喹啉基]-3-吡啶基}苯磺酰胺（GSK 2126458，1）已被鉴定为在药效学和肿瘤生长功效模型中具有体内活性的PI 3 K α和mTOR的高效口服生物可利用抑制剂。化合物1目前正在用于治疗癌症的人类临床试验中进行评价。
Phosphomositide 3-kinase alpha (PI3K alpha) is a critical regulator of cell growth and transformation, and its signaling pathway is the most commonly mutated pathway in human cancers The mammalian target of rapamycin (mTOR), a class IV PI3K protein kinase, is also a central regulator of cell growth, and mTOR inhibitors are believed to augment the antiproliferative efficacy of PI3K/AKT pathway inhibition 2,4-Difluoro-N-{2-(methyloxy)-5-[4-(4-pyridazinyl)-6-quinolinyl]-3-pyridinyl}benzenesulfonamide (GSK2126458, 1) has been identified as a highly potent, orally bioavailable inhibitor of PI3K alpha and mTOR with in vivo activity in both pharrnacodynamic and tumor growth efficacy models Compound 1 is currently being evaluated in human clinical trials for the treatment of cancer.