N-[4-[1-(1,4-二氧杂螺[4.5]癸烷-8-基)-4-(8-氧杂-3-氮杂

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产品名称:N-[4-[1-(1,4-二氧杂螺[4.5]癸烷-8-基)-4-(8-氧杂-3-氮杂双环[3.2.1]辛烷-3-基)-1H-吡唑并[3,4-D]嘧啶-6-基]苯基]-N'-甲基脲

CAS:1144068-46-1

别名：N-[4-[1-(1,4-二氧杂螺[4.5]癸烷-8-基)-4-(8-氧杂-3-氮杂双环[3.2.1]辛烷-3-基)-1H-吡唑并[3,4-D]嘧啶-6-基]苯基]-N'-甲基脲;1-(4-(4-(8-噁-3-氮杂双环[3.2.1]-3-辛基)-1-(1,4-二噁螺[4.5]-8-癸基)-1H-吡唑并[3,4-D]嘧啶-6-基)苯基)-3-甲基脲;WYE-125132(WYE-132);WYE-125132;WYE125132;WYE125132

英文名：N-[4-[1-(1,4-Dioxaspiro[4.5]dec-8-yl)-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]-N'-methylurea

生物活性WYE-125132 (WYE-132)是一种高度有效的，ATP竞争性的mTOR抑制剂，IC50为0.19 nM；作用于mTOR比作用于PI3Ks或PI3K相关激酶hSMG1和ATR选择性高。
体外研究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.
体内研究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.
特征WYE-125132 is a highly potent, ATP-competitive, and specific mTOR kinase inhibitor.