pi3khdac-in-1

Description: PI3K/HDAC-IN-1 is a novel, potent and dual inhibitor of PI3K and HDAC, it potently inhibits PI3Kdelta and HDAC1 with IC50s of 8.1 nM and 1.4 nM, respectively. PI3K/HDAC-IN-1 efficiently modulated the expression of p-AKT and Ac-H3, arrested the cell cycle, and induced apoptosis in HCT116 cancer cells. Following pharmacokinetic studies, PI3K/HDAC-IN-1 was further evaluated in HCT116 and HGC-27 xenograft models to show significant in vivo anticancer efficacies with tumor growth inhibitions of 45.8% (po, 150 mg/kg) and 62.6% (ip, 30 mg/kg), respectively. Overall, this work shows promise in discovering new anticancer therapeutics by the approach of simultaneously targeting PI3K and HDAC pathways with a single molecule.

References: J Med Chem. 2019 Aug 8; 62(15):6992-7014.