VPS34 inhibitor

VPS34 inhibitors are a class of small molecule therapeutics designed to inhibit the activity of vacuolar protein sorting 34 (VPS34), also known as Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3). As a Class III PI3K, VPS34 is essential for the production of phosphatidylinositol 3-phosphate (PI3P), a signaling lipid required for the initiation of autophagy and endosomal trafficking. In oncology, VPS34 inhibition is being investigated as a strategy to disrupt autophagy-mediated survival mechanisms in tumor cells and to enhance anti-tumor immunity by modulating the tumor microenvironment. Preclinical research, including work by Janssen, has demonstrated that VPS34 inhibitors can sensitize drug-resistant castration-resistant prostate cancer (CRPC) cells to anti-androgen therapies, potentially through the downregulation of the androgen receptor (AR) and its variants. Furthermore, VPS34 activation has been identified as a shared molecular mechanism driving pulmonary vascular remodeling in adult pulmonary hypertension and congenital diaphragmatic hernia (CDH), suggesting that VPS34 inhibitors may represent a novel therapeutic approach for these respiratory and cardiovascular conditions.

Other names

VPS34 inhibitorVPS-34 inhibitorVPS 34 inhibitorVPS34 inhibitorsVPS-34 inhibitorsVPS 34 inhibitorsPIK3C3 inhibitorPIK-3C3 inhibitorPIK 3C3 inhibitorClass III PI3K inhibitor