2. Academic Validation
  3. Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349

Discovery and Biological Profiling of Potent and Selective mTOR Inhibitor GDC-0349

  • ACS Med Chem Lett. 2012 Nov 29;4(1):103-7. doi: 10.1021/ml3003132.
Zhonghua Pei 1,  Elizabeth Blackwood 1,  Lichuan Liu 1,  Shiva Malek 1,  Marcia Belvin 1,  Michael F T Koehler 1,  Daniel F Ortwine 1,  Huifen Chen 1,  Frederick Cohen 1,  Jane R Kenny 1,  Philippe Bergeron 1,  Kevin Lau 1,  Cuong Ly 1,  Xianrui Zhao 1,  Anthony A Estrada 1,  Tom Truong 1,  Jennifer A Epler 1,  Jim Nonomiya 1,  Lan Trinh 1,  Steve Sideris 1,  John Lesnick 1,  Linda Bao 1,  Ulka Vijapurkar 1,  Sophie Mukadam 1,  Suzanne Tay 1,  Gauri Deshmukh 1,  Yung-Hsiang Chen 1,  Xiao Ding 1,  Lori S Friedman 1,  Joseph P Lyssikatos 1
Affiliations

Affiliation

  • 1 Departments of Discovery Chemistry, Translational Oncology, DMPK, Biochemical and Cellular Pharmacology, and Pharmaceutics, Genentech, Inc. , 1 DNA Way, South San Francisco, California 94080, United States.
PMID: 24900569 DOI: 10.1021/ml3003132
Abstract

Aberrant activation of the PI3K-Akt-mTOR signaling pathway has been observed in human tumors and tumor cell lines, indicating that these protein kinases may be attractive therapeutic targets for treating Cancer. Optimization of advanced lead 1 culminated in the discovery of clinical development candidate 8h, GDC-0349, a potent and selective ATP-competitive inhibitor of mTOR. GDC-0349 demonstrates pathway modulation and dose-dependent efficacy in mouse xenograft Cancer models.

Keywords

Mammalian target of rapamycin; TDI; mTOR; urea bioisostere.

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