RGNCY-0073 (PI-273 PI4KIIα inhibitor)
PI-273 is the first small molecule inhibitor of PI4KIIα. PI-273 inhibits PI4KIIα kinase activity (IC50 = 0.47 µM) and suppresses MCF-7 and T-47D cell proliferation. Surface plasmon resonance and thermal shift assays indicate that PI-273 interacts directly with PI4KIIα. Kinetic analysis demonstrated that PI-273 is a reversible competitive inhibitor with respect to the substrate PI which contrasts with most other PI kinase inhibitors that bind the ATP binding site. PI-273 reduces PI4P content, cell viability and AKT signalling in wild type MCF-7 cells but not in PI4KIIα knockout MCF-7 cells, indicating that it is highly selective for PI4KIIα. Importantly, PI-273 inhibited MCF-7 cell-induced breast tumor growth in mouse xenograft models without toxicity.
Systematic Name: 2-(3-(4-chlorobenzoyl)thioureido)-4-ethyl-5-methylthiophene-3-carboxamide
Molecular Weight: 381.89
Tags: Cancer, breast cancer, Tumor, MCF-7, RGNCY-0073, PI-273, PI, PI4KIIα