Use of core modification in the discovery of CC214-2, an orally available, selective inhibitor of mTOR kinase PMID: 23414803

ADC Targets in Oncology

2026-04-10

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

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.