17DPG

17DPG, or 17-Demethoxy-17-allylamino-geldanamycin, is a semi-synthetic analog of the antibiotic geldanamycin. It is a member of the ansamycin family of compounds, which are known for their ability to inhibit heat shock protein 90 (Hsp90), a molecular chaperone involved in the folding, stabilization, and activation of numerous client proteins, many of which are involved in signal transduction pathways and cell cycle progression.

The development of 17DPG was motivated by the desire to improve upon the properties of geldanamycin, which, despite its potent anti-tumor activity, exhibits significant toxicity and poor solubility. 17DPG was designed to maintain the Hsp90 inhibitory activity of geldanamycin while reducing its toxicity and enhancing its solubility. The modification involves the removal of the 17-methoxy group and the addition of an allylamino group at the same position.

Preclinical studies have demonstrated that 17DPG exhibits potent anti-proliferative activity against various cancer cell lines, including those resistant to other chemotherapeutic agents. It has been shown to induce the degradation of Hsp90 client proteins, leading to the inhibition of cell growth and induction of apoptosis. Additionally, 17DPG has been found to have improved solubility and reduced toxicity compared to geldanamycin, making it a promising candidate for further development as an anti-cancer agent.

However, the development of 17DPG has been hampered by its limited bioavailability and the rapid development of resistance in cancer cells. Despite these challenges, ongoing research aims to optimize the pharmacological properties of 17DPG and to identify combinations of 17DPG with other anti-cancer agents that may overcome resistance and enhance its therapeutic efficacy.