2220263-80-7

KUNB31 is a selective inhibitor of SP90β with an Kd value of 0.18 μM[1].

KUNB31 is an isoform-selective inhibitor of Hsp90β with an IC50 value of 180 nM and > 50-fold selectivity over closely related isoforms Hsp90α and GRP94.Hsp90 inhibitors currently in clinical trials are all pan-inhibitors with multiple side effects including induction of the pro-survival he at shock response. KUNB31 was shown to induce the degradation of Hsp90β-dependent client proteinsbut not those of Hsp90α and GRP94and did not induce production of Hsp90. It showed anti-proliferative activity against NCI H23 (non-small cell lung cancer)UC3 (bladder cancer)and HT-29 (colon adenocarcinoma) cells with low micromolar IC50 valueswhile requiring more than 100 μM against non-cancerous human embryonic kidney HEK-293 cells.

[1] Lei Wang, et al. Modulation of protein fate decision by small molecules: targeting molecular chaperone machinery. Acta Pharm Sin B. 2020 Oct; 10(10): 1904–1925.