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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 heat shock response. KUNB31 was shown to induce the degradation of Hsp90β-dependent client proteins, but not those of Hsp90α and GRP94, and 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 values, while requiring more than 100 μM against non-cancerous human embryonic kidney HEK-293 cells.

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