GDC-0349

"目录号: HY-15248

PI3K/Akt/mTORAutophagy-

GDC-0349是ATP竞争性mTOR抑制剂，Ki为3.8 nM，比对PI3Kα和其它266种激酶的抑制性高超过700倍。

mTORAutophagy

相关产品

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生物活性

Description

GDC-0349 is a potent and selective ATP-competitive inhibitor of mTOR with Ki of 3.8 nM; >700-fold selectivity over PI3Kα and other 266 kinases.IC50 value: 3.8 nMTarget: mTORGDC-0349 has remarkable selectivity over 266 kinases, including all isoforms of PI3K. GDC-0349 inhibits 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. 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 inhibits tumor growth in a dose-dependent manner. It is also efficacious in other xenograft models, including PC3 (PTEN null) and 786-O (VHL mutant).

Clinical Trial

NCT01356173

Genentech, Inc.

Non-Hodgkin's Lymphoma, Solid Tumor

June 2011

Phase 1

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References

[1].Zhonghua Pei, et al. Pyrimidoaminotropanes as potent, selective, and efficacious small molecule kinase inhibitors of the mammalian target of rapamycin (mTOR). J Med Chem, 2013, 56(7), 3090-3101.

[2].Zhonghua Pei, et al. Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349. ACS Med Chem Lett. 2013 Jan 10; 4(1): 103–107.