Geldanamycin (GA) is a natural product produced by Streptomyces hygroscopicus. GA binds with high affinity into the ATP binding pocket of Hsp90. Hsp90 is a ubiquitous molecular chaperone critical for the folding, assembly and activity of multiple mutated and overexpressed signaling proteins that promote the growth and/or survival of tumor cells. Hsp90 client proteins include mutated p53, Raf-1, Akt, ErbB2 and hypoxia-inducible factor 1a (HIF-1a). Binding of GA to Hsp90 causes the destabilization and degradation of its client proteins.

[1] Roe SM, et al. Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J Med Chem.1999, 42(2):260-266.

[2] Neckers L. Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med. 2002,8(4 Suppl):55-61.

[3] Whitesell L. et al. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. PNAS.1994, 91(18):8324-8328.