FD223

FD223 is a potent and selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor developed through a bioisosteric replacement approach based on an indole scaffold. It is being studied for the treatment of acute myeloid leukemia (AML). In vitro studies demonstrated high potency (IC50 = 1 nM) and selectivity (29-51 fold over other PI3K isoforms) against PI3Kδ. FD223 effectively inhibits the proliferation of AML cell lines (MOLM-16, HL-60, EOL-1, and KG-1) by suppressing p-AKT Ser473, leading to G1 phase arrest during the cell cycle. In vivo studies in nude mice xenograft models confirmed significant antitumor efficacy with no observable toxicity, comparable to Idelalisib (CAL-101), indicating its potential for further development as a promising PI3Kδ inhibitor for leukemia such as AML.