1. Rational Design, Synthesis, and SAR of a Novel Thiazolopyrimidinone Series of Selective PI3K-beta Inhibitors
- Author
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Hong Lin, Charles B. Davis, Kaushik Raha, Ralph A. Rivero, Michael D. Schaber, Jeanelle McSurdy-Freed, Mary Ann Hardwicke, Karl F. Erhard, James F. Mack, Ren Xie, Michael D. Spengler, Ramona Plant, Cynthia M. Rominger, Junya Qu, Rosanna Tedesco, Jennifer L. Ariazi, Juan I. Luengo, Mark J. Schulz, Michael D. Squire, Christian S. Sherk, and Jin Zeng
- Subjects
business.industry ,Organic Chemistry ,Rational design ,medicine.disease ,Bioinformatics ,Biochemistry ,Prostate cancer ,chemistry.chemical_compound ,chemistry ,Breast cancer cell line ,Drug Discovery ,Cancer research ,Medicine ,Structure–activity relationship ,Homology modeling ,Growth inhibition ,business ,Beta (finance) ,PI3K/AKT/mTOR pathway - Abstract
A novel thiazolopyrimidinone series of PI3K-beta selective inhibitors has been identified. This chemotype has provided an excellent tool compound, 18, that showed potent growth inhibition in the PTEN-deficient breast cancer cell line MDA-MB-468 under anchorage-independent conditions, and it also demonstrated pharmacodynamic effects and efficacy in a PTEN-deficient prostate cancer PC-3 xenograft mouse model.
- Published
- 2012