VPS34-IN1

VPS34-IN1 is a potent and highly selective small molecule inhibitor of the Class III phosphoinositide 3-kinase (PI3K), also known as vacuolar protein sorting 34 (VPS34) or PIK3C3. Developed by Novartis, it inhibits VPS34 with nanomolar potency (IC50 approximately 25 nM) while exhibiting minimal activity against other PI3K isoforms or a broad panel of protein kinases. By rapidly depleting the cellular pool of phosphatidylinositol 3-phosphate (PI3P) at endosomal membranes, VPS34-IN1 disrupts macroautophagy, endosomal recycling, and vesicular trafficking. Preclinical studies have demonstrated its potential as an antineoplastic agent in acute myeloid leukemia (AML) and breast cancer, where it induces apoptosis and energy stress. Furthermore, VPS34-IN1 has shown promise in enhancing STING-dependent immune responses and inhibiting the replication of viruses such as SARS-CoV-2 and murine cytomegalovirus (MCMV).

Other names

PIK3C3-IN1PIK-3C3-IN1PIK 3C3-IN1