Identification of Inhibitors of the Lipid Kinase PI5P4Ka/B as Potential Anti-Cancer Agents

National Center For Advancing Translational Sciences

Investigators

Abstract

The collaborative team previously uncovered novel inhibitors of the lipid kinase PI5P4Ka/B as potential anti-cancer agents. After an extensive SAR campaign against PI5P4Ka and b, the team demonstrated that a key dual PI5P4Ka/b inhibitor can kill p53 mutant cancer cells under conditions where autophagy is upregulated. A CBC (NCI) funded SAR campaign was conducted to develop dual inhibitors of PI5P4K alpha and beta. The team also developed PROTACs to further explore the intended therapeutic modality. Studies that correlate target modulation by inhibition or degradation with expected phenotypes are still ongoing.