GDC-0349

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

GDC-0349 是一种有效的选择性 ATP 竞争性 mTOR 抑制剂，Ki 为 3.8 nM，对 PI3Kα 和其他 266 种激酶具有 790 倍的抑制作用。

GDC-0349 is a small molecule anticaner drug candidate, being developed by Genentech. As of July 2012, Genentech has filed phase I trial of GDC-0349 for evaluating the Safety and Tolerability of GDC-0349 in Patients With Locally Advanced or Metastatic Solid Tumors or Non Hodgkin's Lymphoma.

GDC-0349 (Compound 8h) is a remarkably selective mTOR inhibitor, with less than 25% inhibition of 266 kinases, including all isoforms of PI3K when tested at 1 μM.

When dosed orally once daily in athymic mice in a MCF7-neo/Her2 tumor xenograft model (PI3K mutation), GDC-0349 (Compound 8h) inhibits tumor growth in a dose-dependent manner, achieving stasis (99% TGI) at the maximum tolerated dose. Body weight change is less than 10% up to the highest dose. GDC-0349 is also efficacious in other xenograft models, including PC3 (PTEN null) and 786-0 (VHL mutant). Similar levels of tumor growth inhibition are achieved when GDC-0349 is administered once every three days at higher doses compared to once every day. GDC-0349 has ~10-fold reduced free plasma clearance in both mice (100 mL/min/kg) and rats (171 mL/min/kg in rat).

GDC0349 | GDC 0349 | GDC-0349 | RG7603

MAPK/ERK Signaling

Raf

mTOR| PI3Kα

Cancer

——

1207360-89-1

452.55

C24H32N6O3

>98% (HPLC)

DMSO : ≥ 100 mg/mL. 220.97 mM

CCNC(=O)NC1=CC=C(C=C1)C1=NC(N2CCOC[C@@H]2C)=C2CCN(CC2=N1)C1COC1

(S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-7-(oxetan-3-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea

(-20℃)

With Ice Pack

≥ 2 years