17-N-allylamino-17-demethoxygeldanamycin
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Chemical Data
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17-N-Allylamino-17-demethoxygeldanamycin (17-AAG) is a semi-synthetic derivative of the antibiotic geldanamycin, which is an Hsp90 inhibitor. It is primarily studied for its potential use as an anticancer agent.
Mechanism of Action[edit | edit source]
17-AAG functions by inhibiting the heat shock protein 90 (Hsp90), a molecular chaperone that is involved in the proper folding, stability, and function of many oncoproteins. By inhibiting Hsp90, 17-AAG causes the degradation of these client proteins, leading to the disruption of multiple signaling pathways that are essential for cancer cell growth and survival.
Clinical Development[edit | edit source]
17-AAG has been evaluated in several clinical trials for the treatment of various types of cancer, including breast cancer, prostate cancer, and melanoma. Although it showed promise in preclinical studies, its clinical development has been challenging due to issues related to its formulation, stability, and toxicity.
Pharmacokinetics[edit | edit source]
The pharmacokinetics of 17-AAG are complex due to its poor solubility and stability. It is metabolized in the liver and has a relatively short half-life. Efforts have been made to develop more stable and soluble formulations to improve its bioavailability and therapeutic index.
Side Effects[edit | edit source]
The side effects of 17-AAG are similar to those of other Hsp90 inhibitors and may include hepatotoxicity, gastrointestinal disturbances, and fatigue.
Research and Future Directions[edit | edit source]
Research continues to explore the potential of 17-AAG in combination with other anticancer agents, as well as its use in targeting specific cancer subtypes. Newer analogs and formulations are also being developed to overcome the limitations of 17-AAG.
Also see[edit | edit source]
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Contributors: Bonnu, Prab R. Tumpati, MD
