来宝网移动站

mTOR是参与PI3K信号通路的很重要的因子，今天就来介绍一下它的功能和相关的抑制剂。

先上一张有关mTOR信号通路图



Mammalian target of rapamycin（mTOR）：哺乳动物雷帕霉素靶蛋白

是 一种存在于哺乳动物细胞中的Ser/Thr激酶。近年来大量研究表明mTOR与人体炎症、损伤、增生、组织修复、纤维化以及肿瘤发生发展等一系列重要的病 理生理过程密切相关。深入的研究也证实mTOR可通过汇聚和整合来自于营养、生长因子、能量和环境胁迫对细胞的刺激信号，进而调节细胞生长。因此对 mTOR进行抑制是治疗与该通路密切相关的肿瘤包括肾癌、淋巴瘤、肺癌、肝癌、乳腺癌、神经内分泌癌和胃癌等的靶点。

其与参与PI3K通 路的主要机制如下：PDK1通过PI3K通路在Thr308位点活化，然后被激活的mTORC2在Ser473位点完全活化。PRAS40可以抑制 mTORC1使其失活，AKT可直接磷酸化PRAS40，使其对mTORC1的抑制作用失效，从而激活mTORC1通路。另外，AKT还可以通过磷酸化并 抑制TSC1/TSC2二聚体从而将mTOR活化。随后mTOR可以通过磷酸化其下游蛋白S6K1和4E-BP来调节下游蛋白质翻译。

下面是主要的高特异性抑制剂：

AZD8055

AZD8055 is a potent'' selective'' and orally bioavailable ATP-competitive mTOR kinase inhibitor with an IC50 of 0.8 nM.

Deforolimus (Ridaforolimus)

Deforolimus (Ridaforolimus) is a small-molecule inhibitor of mTOR.

Everolimus (RAD001)

Everolimus (RAD001) also known as SDZ-RAD'' Certican'' Zortress'' Afinitorm is MTOR inhibitor available at Selleck with IC50 of 0.63 nM.

OSI-027

OSI027 is a potent mammalian target of rapamycin (mTOR) kinase inhibitor.

PP242

PP242 is a novel potent and selective mTOR inhibitor with an IC50 of 8 nM.

Rapamycin (Sirolimus)

Rapamycin also known as Sirolimus & Rapamune is a mTOR inhibitor. Rapamycin Sirolimus inhibits cell motility by suppression of mTOR-mediated pathways.

Temsirolimus (Torisel)

Temsirolimus (Torisel) is a mTOR inhibitor.

WAY-600

WAY-600 is a potent ATP-competitive mTOR inhibitor with an IC50 of 9 nM.

WYE-125132

WYE-125132 is a highly potent'' ATP-competitive and specific mTOR kinase inhibitor with an IC50 of 0.19 nM.

WYE-354

WYE-354 is a mTOR inhibitor with an IC50 of 5 nM.

WYE-687

WYE-687 is a potent ATP-competitive mTOR inhibitor with an IC50 of 7 nM.