17-AAG

17-AAG

17-AAG (17-Allylamino-17-demethoxygeldanamycin) is a derivative of the antibiotic geldanamycin, which is an inhibitor of heat shock protein 90 (Hsp90). It is primarily studied for its potential use in cancer treatment due to its ability to interfere with the function of Hsp90, a protein that stabilizes several proteins required for tumor growth.

Mechanism of Action

17-AAG binds to the ATP-binding pocket of Hsp90, inhibiting its activity. This inhibition leads to the degradation of client proteins that are essential for the growth and survival of cancer cells. By disrupting the function of Hsp90, 17-AAG can induce the degradation of oncogenic proteins such as HER2/neu, BCR-ABL, and mutant p53, leading to the inhibition of cancer cell proliferation and induction of apoptosis.

Clinical Development

17-AAG has been evaluated in several clinical trials for its efficacy in treating various types of cancer, including breast cancer, lung cancer, and melanoma. While it has shown promise in preclinical studies, its clinical development has faced challenges, including issues related to its formulation and toxicity.

Related Compounds

Other derivatives of geldanamycin, such as 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin), have also been developed to improve the pharmacological properties and reduce the toxicity associated with 17-AAG.

See Also

• Geldanamycin
• Heat shock protein 90
• Cancer treatment
• Clinical trials