KW-2478 + bortezomib

KW-2478 + bortezomib is a **combination therapy** evaluated for the treatment of relapsed and/or refractory multiple myeloma. **KW-2478** is a novel, non-ansamycin, small-molecule inhibitor of heat shock protein 90 (Hsp90), a molecular chaperone involved in the stability and function of multiple oncogenic client proteins. **Bortezomib** is a first-in-class small-molecule **proteasome inhibitor** that targets the chymotrypsin-like activity of the 26S proteasome in mammalian cells, leading to disrupted protein degradation, cell cycle arrest, and apoptosis, particularly in hematologic malignancies. Preclinical and clinical studies have shown that the two agents act synergistically: KW-2478 enhances the anti-myeloma effects of bortezomib by impairing cellular stress response and protein homeostasis mechanisms, thereby increasing proteotoxic stress and apoptosis of myeloma cells. Clinical trials found that this combination had a modest but notable response rate (objective response rate ~39%) and was generally well-tolerated, with no significant overlapping toxicities or unusual adverse event profiles beyond those typical for the individual agents[1][4][5][6][7].

Other names

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