WYE-125132 (WYE-132)是一種高度有效的，ATP競(jìng)爭(zhēng)性的mTOR抑制劑，IC50為0.19 nM；作用于mTOR比作用于PI3Ks或PI3K相關(guān)激酶hSMG1和ATR選擇性高。WYE-125132 potently and ATP-competitively inhibits recombinant mTOR kinase with IC50 of 0.19 nM and also shows the high selectivity over various PI3Ks and a panel of 230 protein kinases. In vitro, WYE-125132 exhibits a significant anti-proliferative activity against a panel of tumor cell lines with IC50 ranging from 2 nM (LNCap) to 380 nM (HTC116). Besides, WYE-125132 also causes cell cycle progression, induction of apoptosis, and inhibition of protein synthesis and cell size. WYE-125132 results in a significant reduction in the synthesis of pre-tRNA^Leu by 72%, 80%, and 53% in actively proliferating cells of MG63, MDA361, and HEK293, respectively by inhibiting mTORC1. Moreover, WYE-125132 is also found to induce the dephosphorylation of Maf1 (negative regulator of Pol III transcription) and its accumulation in the nucleus.WYE-125132 (5 mg/kg p.o.) produces significant antitumor activity and causes dose-dependent tumor growth delay in the PI3K/mTOR- and HER2-hyperactive MDA361 tumor model. In addition, WYE-125132 also shows potent antitumor efficacy in the PTEN-null glioma U87MG, non-small cell lung cancer H1975 and A549 models.WYE-125132 is a highly potent, ATP-competitive, and specific mTOR kinase inhibitor.WYE-125132 (WYE-132)是一種高度有效的，ATP競(jìng)爭(zhēng)性的mTOR抑制劑，IC50為0.19 nM；作用于mTOR比作用于PI3Ks或PI3K相關(guān)激酶hSMG1和ATR選擇性高。

Target	Value
mTOR (Cell-free assay)	0.19 nM

WYE-125132強(qiáng)效且ATP競(jìng)爭(zhēng)性抑制重組mTOR激酶，IC50 為0.19 nM，選擇性比作用于各種PI3Ks和230個(gè)蛋白激酶組高。在體外，WYE-125132對(duì)一組腫瘤細(xì)胞系表現(xiàn)出顯著的抗增殖活性，IC50 范圍為2 nM (LNCap) 到380 nM (HTC116)。此外，WYE-125132也會(huì)引起細(xì)胞周期進(jìn)程，細(xì)胞凋亡誘導(dǎo)，以及蛋白合成和細(xì)胞大小的抑制。 WYE-125132通過(guò)抑制mTORC1引起pre-tRNA

在PI3K/mTOR- 和HER2-極度活躍的MDA361腫瘤模型中，WYE-125132(5 mg/kg p.o.)產(chǎn)生顯著的抗腫瘤活性，并引起腫瘤生長(zhǎng)劑量依賴性延緩。此外，WYE-125132在PTEN缺失的膠質(zhì)瘤U87MG，非小細(xì)胞肺癌H1975 和A549模型中表現(xiàn)出有效的抗腫瘤活性。