WK88-1

WK88-1 is a non-benzoquinone, reblastatin-derived geldanamycin analog that functions as a potent and selective inhibitor of the molecular chaperone **heat shock protein 90 (Hsp90)**. It was rationally designed to circumvent the hepatotoxicity associated with benzoquinone-containing geldanamycin derivatives. WK88-1 induces degradation of multiple Hsp90 client proteins—including **EGFR**, **ErbB2**, **ErbB3**, **Met**, and **Akt**—resulting in inhibition of proliferation, migration, and invasion, as well as induction of apoptosis in gefitinib-resistant non-small cell lung cancer (NSCLC) cell lines harboring EGFR T790M or Met-amplification mutations. Preclinical studies showed WK88-1 can significantly reduce tumor growth in xenograft mouse models of gefitinib-resistant NSCLC, without inducing significant hepatotoxicity[1][2][5].