GDC-0349 1207360-89-1

GDC-0349  1207360-89-1

 GDC0349
分子式：C24H32N6O3  分子量：452.55
 
产品描述
GDC-0349 是有效的，选择性的，ATP竞争性mTOR抑制剂，Ki为3.8 nM,比作用于PI3Kα和其他266种激酶的抑制效果高790倍。
靶点
     
IC50
     
体外研究
GDC-0349 is a potent and selective ATP-competitive inhibitor of mTOR with IC50 ~3.8 nM. It has remarkable selectivity over 266 kinases, including all isoforms of PI3K (less than 25% inhibition when tested at 1 μM against Invitrogen kinase panel).
体内研究
GDC-0349 demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft cancer models.  When dosed orally once daily in athymic mice in a MCF7-neo/Her2 tumor xenograft model (PI3K mutation), GDC-0349 inhibited tumor growth in a dose-dependent manner. It was also efficacious in other xenograft models, including PC3 (PTEN null) and 786-0 (VHL mutant). GDC-0349 inhibited downstream markers of mTOR, including phospho-4EBP1 and phospho-Akt(S473) in an in vivo PK/PD study in mouse, consistent with an inhibition of both mTORC1 and mTORC2 complexes. Currently GDC-0349 is in Phase I clinical trials to evaluate the safety and tolerability in patients with locally advanced or metastatic solid tumors or Non-Hodgkin's lymphoma.
溶解性
DMSO 91 mg/mL，水 <1 mg/mL，乙醇 6 mg/mL
稳定性
2年 -20°C粉状，6月-80°C溶于DMSO