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.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.
