KW-2478 is a novel and potent nonansamycin inhibitor of heat shock protein 90 (Hsp90) to overcome the limitations, including low water solubility and hepatotoxicity, of 17-allylamino-17-demethoxygeldanamycin (17-AAG). KW-2478 exerts a strong antitumor activity against multiple myeloma (MM) cells with various chromosormal translocation, in which KW-2478 inhibits cell growth and apoptosis associated with Hsp90 client protein degradation and the decreasing of IgH translocation products including FGFR3, c-Maf and cyclin D1. Recent study results have revealed that KW-2478 is able to deplete Hsp90 client Cdk9 and the phosphorylated 4E-BP1, a transcriptional kinase and a transcription inhibitor respectively, leading to the reduced expression of c-Maf and cyclin D1.

Reference

[1].Nakashima T, Ishii T, Tagaya H, Seike T, Nakagawa H, Kanda Y, Akinaga S, Soga S, Shiotsu Y. New molecular and biological mechanism of antitumor activities of KW-2478, a novel nonansamycin heat shock protein 90 inhibitor, in multiple myeloma cells. Clin Cancer Res. 2010; 16(10): 2792-802.

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