The heat shock proteins (Hsps) act as molecular chaperones. Hsp90 is an abundant protein with roles in protein folding, cell signaling, and cancer. VER-49009 is a pyrazole compound that inhibits Hsp90 with an IC50 value of 47 nM. It produces a cellular antiproliferative GI50 value of 685 nM when tested against a human cancer cell line panel. Consistent with inhibition of Hsp90, VER-49009 induces the expression of Hsp27 and Hsp72 while reducing the client proteins c-Raf, B-Raf, survivin, and PRMT5, causing cell cycle arrest and apoptosis.
