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Updated: Jun 9, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
4-methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors
Kevin K-C Liu1, Shubha Bagrodia, Simon Bailey
1Pfizer Global Research and Development, Chemistry Department, La Jolla, CA 92120, USA. kevin.k.liu@pfizer.com
Abstract:
Pteridinones were designed based on a non-selective kinase template. Because of the uniqueness of the PI3K and mTOR binding pockets, a methyl group was introduced to C-4 position of the peteridinone core to give compounds with excellent selectivity for PI3K and mTOR. This series of compounds were further optimized to improve their potency against PI3Kα and mTOR. Finally, orally active compounds with improved solubility and robust in vivo efficacy in tumor growth inhibition were identified as well.
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