CZ415 is a potent and highly selective mTOR inhibitor.

mTOR:8.07(pIC50)

CZ415具有优良的细胞渗透性，未显示出任何遗传毒性。CZ415的处理可抑制mTORC1和mTORC2下游靶点的磷酸化（对pS6RP的IC50=14.5 nM，对pAKT的IC50=14.8 nM）。通过检测刺激后的人全血中分泌的IFNγ，测定CZ415的免疫抑制效应，其IC50为226 nM。CZ415未展示遗传毒性潜能，既不在细菌突变试验（Ames试验）中显现突变性，也不在有或无大鼠肝S9混合物的情况下，在小鼠淋巴瘤试验（MLA）中显示遗传毒性[1]。

体内研究显示，CZ415具有中等清除率和良好的口服生物利用度。在抗CD3小鼠模型中，CZ415有效抑制mTOR下游信号传导；在CIA小鼠模型中，显示出显著的抗炎作用。凭借其卓越的选择性、药物样性质以及体内证实的疗效，CZ415被视为药理学研究mTOR在体内病理生理作用的理想分子[1]。

Cells are seeded in 90 μL DMEM containing 2% FCS at 4x104 cells/well (for pS6RP S240/244 assay) or 8x104 cells/well (for pAKT S473 assay) in a 96well U-bottom plate. The plate is then incubated for 1h in a humidified incubator (37oC, 5% CO2) to allow cells to adhere. CZ415: 3 μM start, 8 points 1:3 dilution steps, n=2. Positive control: 1 μM PI-103 (n=8). Negative control: DMSO (n=8). 10 μL of 10x compound concentration in 1% DMSO/99% (DMEM 2% FCS) are added to the cells followed by 2 h incubation in a humidified incubator (37oC, 5% CO2). Cells are lysed by addition of 10 μL 5x Complete Lysis Buffer and gentle shaking at 4°C for 15 min (Only for Reference)