Sigma-Aldrich ZSTK474，≥98%（HPLC）

产品概述

经口给药对小鼠实体瘤和人癌症异种移植物的强效抗肿瘤活性

生化/生理作用

A novel s-triazine derivative, ZSTK474 [2-(2-difluoromethylbenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine], strongly inhibited the growth of tumor cells. A molecular target for ZSTK474 is PI3K. ZSTK474 directly inhibits PI3K activity more efficiently than the PI3K inhibitor LY294002. At concentrations of 1μM, ZSTK474 and LY2194002 reduced PI3K activity to 4.7% (95% confidence interval [CI] = 3.2% to 6.1%) and 44.6% (95% CI = 38.9% to 50.3%), respectively, of the untreated control level. Molecular modeling of the PI3K-ZSTK474 complex indicated that ZSTK474 could bind to the ATP-binding pocket of PI3K. ZSTK474 inhibited phosphorylation of signaling components downstream from PI3K, such as Akt and glycogen synthase kinase 3β, and mediated a decrease in cyclin D1 levels. ZSTK474 administered orally to mice had strong antitumor activity against human cancer xenografts without toxic effects in critical organs. Akt phosphorylation was reduced in xenograft tumors after oral administration of ZSTK474. ZSTK474 is a new PI3K inhibitor with strong antitumor activity against human cancer xenografts without toxic effects in critical organs.

ZSTK 474是一种可逆的PI3K抑制剂，IC50 10 - 100 nM，可降低小鼠胚胎成纤维细胞PDGF依赖的膜皱褶，抑制PI3K下游组分Akt和糖原合成酶激酶-3 β的磷酸化，降低细胞周期蛋白D1水平。

ZSTK 474是一种口服活性、强效和选择性的ATP竞争性抑制剂，可抑制I类磷脂酰肌醇3激酶亚型（PI3K IC 50（nM）= 4.6/δ，16/α，44/β，49/γ，ATP = 10 μM; mTOR IC 50>100 μM），对PI 3 K α的选择性是DNA-PK的27倍。ZSTK 474抑制培养物中A549细胞中PI 3 K介导的信号传导事件（0.5 μM; Akt pSer 473、GSK-3β pSer 9、cyclinD 1表达）并在体内诱导小鼠肿瘤生长停滞或消退（100、200或400 mg/kg，每日口服，抗鼠B16 F10黑色素瘤或人A549肺癌、PC-3前列腺癌和WiDr结肠癌）。

技术规格