alvespimycin

Alvespimycin (KOS-1022) is a semi-synthetic derivative of the antibiotic geldanamycin and acts as a potent inhibitor of Heat Shock Protein 90 (Hsp90). By binding to the ATP-binding pocket of Hsp90, alvespimycin disrupts the chaperone function of the protein, leading to the proteasomal degradation of various client proteins essential for tumor cell survival and proliferation, such as HER2, Akt, and Raf-1. Originally developed by Kosan Biosciences and later acquired by Bristol Myers Squibb, it was primarily investigated for the treatment of HER2-positive metastatic breast cancer and acute myeloid leukemia. Clinical development for breast cancer reached Phase 2, but the program was eventually discontinued.

Other names

17-dimethylaminoethylamino-17-demethoxygeldanamycin