1144068-46-1
中文名稱
N-[4-[1-(1,4-二氧雜螺[4.5]癸烷-8-基)-4-(8-氧雜-3-氮雜雙環(huán)[3.2.1]辛烷-3-基)-1H-吡唑并[3,4-D]嘧啶-6-基]苯基]-N'-甲基脲
英文名稱
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
CAS
1144068-46-1
分子式
C27H33N7O4
分子量
519.595
MOL 文件
1144068-46-1.mol
更新日期
2024/11/13 09:56:00
1144068-46-1 結構式
基本信息
中文別名
MTOR抑制劑(WYE-125132)1-(4-(4-(8-噁-3-氮雜雙環(huán)[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
N-[4-[1-(1,4-二氧雜螺[4.5]癸烷-8-基)-4-(8-氧雜-3-氮雜雙環(huán)[3.2.1]辛烷-3-基)-1H-吡唑并[3,4-D]嘧啶-6-基]苯基]-N'-甲基脲
英文別名
WYE-132WYE 125132
WYE 125132(WYE-132)
WYE-132 (WYE-125132)
WYE-125132
WYE 125132
WYE125132/WYE-125132/WYE-132
WYE-125132 (WYE-132)
WYE-125132
WYE 125132
WYE125132
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
1-[4-(1-{1,4-dioxaspiro[4.5]decan-8-yl}-4-{8-oxa-3-azabicyclo[3.2.1]octan-3-yl}pyrazolo[3,4-d]pyrimidin-6-yl)phenyl]-3-methylurea
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
所屬類別
生物化工：mTOR 抑制劑物理化學性質(zhì)
熔點162-184°C (dec.)
密度1.55
儲存條件-20°C冷凍
溶解度二甲基亞砜（微溶）
酸度系數(shù)(pKa)13.82±0.46(Predicted)
形態(tài)白色粉末狀固體。
顏色灰白色至淺米色
常見問題列表
生物活性
WYE-125132 (WYE-132)是一種高度有效的，ATP競爭性的mTOR抑制劑，IC50為0.19 nM；作用于mTOR比作用于PI3Ks或PI3K相關激酶hSMG1和ATR選擇性高。體外研究
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-tRNALeu 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.體內(nèi)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.靶點
| Target | Value |
|
mTOR
(Cell-free assay) | 0.19 nM |
體外研究
WYE-125132強效且ATP競爭性抑制重組mTOR激酶，IC50 為0.19 nM，選擇性比作用于各種PI3Ks和230個蛋白激酶組高。在體外，WYE-125132對一組腫瘤細胞系表現(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也會引起細胞周期進程，細胞凋亡誘導，以及蛋白合成和細胞大小的抑制。 WYE-125132通過抑制mTORC1引起pre-tRNA
體內(nèi)研究
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，并引起腫瘤生長劑量依賴性延緩。此外，WYE-125132在PTEN缺失的膠質(zhì)瘤U87MG，非小細胞肺癌H1975 和A549模型中表現(xiàn)出有效的抗腫瘤活性。