1144068-46-1
中文名称
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
英文名称
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
2024/05/06 18:22:36
1144068-46-1 结构式
基本信息
中文别名
MTOR抑制剂(WYE-125132)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
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
英文别名
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
所属类别
生物化工：mTOR 抑制剂物理化学性质
熔点162-184°C (dec.)
密度1.55
储存条件-20°C冷冻
溶解度二甲基亚砜（微溶）
酸度系数(pKa)13.82±0.46(Predicted)
形态白色粉末状固体。
颜色灰白色至浅米色
常见问题列表
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-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.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.靶点
| Target | Value |
|
mTOR
(Cell-free assay) | 0.19 nM |
体外研究
WYE-125132强效且ATP竞争性抑制重组mTOR激酶，IC50 为0.19 nM，选择性比作用于各种PI3Ks和230个蛋白激酶组高。在体外，WYE-125132对一组肿瘤细胞系表现出显著的抗增殖活性，IC50 范围为2 nM (LNCap) 到380 nM (HTC116)。此外，WYE-125132也会引起细胞周期进程，细胞凋亡诱导，以及蛋白合成和细胞大小的抑制。 WYE-125132通过抑制mTORC1引起pre-tRNA
体内研究
在PI3K/mTOR- 和HER2-极度活跃的MDA361肿瘤模型中，WYE-125132(5 mg/kg p.o.)产生显著的抗肿瘤活性，并引起肿瘤生长剂量依赖性延缓。此外，WYE-125132在PTEN缺失的胶质瘤U87MG，非小细胞肺癌H1975 和A549模型中表现出有效的抗肿瘤活性。