Phosphoinositide 3-kinase (PI3K) pathway activation plays a major role in cancer as a result of abnormalities in major components of this signalling cascade, including activating point mutations and/or amplification of the PIK3CA gene, as well as loss of negative regulatory proteins such as Phosphatase and TENsin homologue (PTEN). It has been reported that conditional knock-out of PIK3CB, and not PIK3CA, leads to tumor growth inhibition in PTEN-deficient genetic context, as well as to prevent prostate tumor formation induced by PTEN loss with concomitant diminution of AKT phosphorylation. We report herein the discovery and optimization of a novel series of PI3Kb isoform-selective small molecular mass inhibitors and their potential application as anti-cancer agents in PTEN-deficient tumors.

Discovery and optimization of pyrimidone PI3Kß inhibitors

245th National Meeting (2013)

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