KUNB31

KUNB31 is an isoform-selective potent inhibitor of HSP90beta with an IC50 value of 180 nM and > 50-fold selectivity over the isoforms HSP90alpha and GRP94. KUNB31 was shown to induce the degradation of HSP90beta-dependent client proteins, but not those of Hsp90alpha and GRP94. It showed anti-proliferative activity against NCI H23 (non-small cell lung cancer), UC3 (bladder cancer) and HT-29 (colon adenocarcinoma) cells. KUNB31 specificly induces the degradation of HSP90beta-dependent client proteins (EGFR, HER2, CDK4, CDK6, CXCR4 etc.) in cells. Heat-shock protein 90 (HSP90) is an abundant protein involved in many cellular signaling processes, including inflammation. HSP90 binds NLRP3 and regulates inflammasome activation and IL-1beta secretion. HSP90 inhibitors are used to inhibit NLRP3-dependent inflammation and study inflammasome responses in disease. Recently, it has been shown that while NLRP3 WT does not need HSP90beta, mutated NLRP3 proteins (except E567K) that are autoactivated and responsible for the disease cryopyrin-associated periodic syndromes (CAPS) need the chaperone HSP90beta during their autoactivation. KUNB31 is used as a selective HSP90beta inhibitor in such NLRP3 inflammasome studies to inhibit NLRP3 activity.