2. Academic Validation
  3. Use of core modification in the discovery of CC214-2, an orally available, selective inhibitor of mTOR kinase

Use of core modification in the discovery of CC214-2, an orally available, selective inhibitor of mTOR kinase

  • Bioorg Med Chem Lett. 2013 Mar 15;23(6):1588-91. doi: 10.1016/j.bmcl.2013.01.110.
Deborah S Mortensen 1,  John Sapienza,  Branden G S Lee,  Sophie M Perrin-Ninkovic,  Roy Harris,  Graziella Shevlin,  Jason S Parnes,  Brandon Whitefield,  Matt Hickman,  Gody Khambatta,  Rene R Bisonette,  Sophie Peng,  Jim C Gamez,  Jim Leisten,  Rama Krishna Narla,  Kimberly E Fultz,  Sabita Sankar
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Celgene Corporation, 4550 Towne Centre Court, San Diego, CA 92121, United States. dmortens@celgene.com
PMID: 23414803 DOI: 10.1016/j.bmcl.2013.01.110
Abstract

We report here the discovery of a novel series of selective mTOR kinase inhibitors and the identification of CC214-2, a compound with demonstrated anti-tumor activity upon oral dosing in a PC3 prostate Cancer xenograft model. A series of 4,6-disubstituted-3,4-dihydropyrazino[2,3-b]pyrazine-2(1H)-ones were discovered through a core modification of our original compound series. Analogs from this series have excellent mTOR potency and maintain selectivity over the related PI3Kα lipid kinase. Compounds such as CC214-2 were found to block both mTORC1(pS6) and mTORC2(pAktS473) signaling in PC3 Cancer cells, in vitro and in vivo.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-154910
    mTOR Inhibitor