PI3K/mTOR抑制剂-1

PI3K/mTOR Inhibitor-1 是一种有效的,口服生物可利用的双重 PI3K/mTOR 抑制剂,抑制 PI3Kα/PI3Kβ/PI3Kγ/PI3Kδ 和 mTOR,IC50 分别为 20/376/204/46 nM 和 186 nM。具有抗肿瘤活性。

研究领域 >> 癌症

信号通路 >> PI3K/Akt/mTOR 信号通路 >> PI3K

PI3Kα:20 nM (IC50)

PI3Kβ:376 nM (IC50)

PI3Kγ:204 nM (IC50)

PI3Kδ:46 nM (IC50)

mTOR:186 nM (IC50)

PI3K/mTOR抑制剂-1(化合物26)也显示出对AKT磷酸化的有效功能抑制(IC50 = 196nM),并且对一组癌细胞具有优异的抗增殖作用[1]。 PI3K/mTOR抑制剂-1对一组癌细胞表现出优异的抗增殖作用。 PI3K/mTOR抑制剂抑制A431,A549,PC3,MDA-MB-361,SW480,ES-2,HT29,SK-OV-3,HCT116,G401,BT20,DLD1 HCC827,H1650,H460,Farage,H820,HCT15, H358,Colo-205,PC9,H1975,WSU-DLCL2,HT,A2780,SU-DHL-10,Toledo,SU-DHL-6,DB和Pfeiffer细胞,IC50为0.188,0.104,0.063,0.085,0.534, 0.179,0.163,0.135,0.308,0.113,0.727,0.264,0.287,1.662,0.611,0.202,0.365,0.104,0.098,0.109,0.237,0.136,0.145,0.090,0.251,0.215,0.269,0.111,0.062,0.061μM,分别[1]。

PI3K/mTOR抑制剂-1(化合物26)产生54.4％的肿瘤生长抑制(TGI),每日口服剂量为3.75mg/kg,持续27天。 7.5mg/kg组的PI3K/mTOR抑制剂-1显示出更显着的TGI(72.9％)。所有动物在治疗27天后存活,而在PI3K/mTOR抑制剂-1,7.5mg/kg组中观察到15％的体重减轻[1]。

[1]. Shen S, et al. Discovery of an Orally Bioavailable Dual PI3K/mTOR Inhibitor Based on Sulfonyl-Substituted Morpholinopyrimidines. ACS Med Chem Lett. 2018 Jun 25;9(7):719-724.