retaspimycin

Retaspimycin hydrochloride, also known by its developmental code IPI-504, is a water-soluble prodrug of tanespimycin (17-AAG) designed for intravenous use. As an inhibitor of heat shock protein 90 (HSP90), retaspimycin targets a molecular chaperone essential for the stability and function of numerous client oncoproteins, including hormone receptors and kinases such as HER2, BCR-ABL, and AKT. By inhibiting HSP90, retaspimycin promotes the proteasomal degradation of these client proteins, disrupting signaling pathways that support tumor cell survival and potentially inducing cell cycle arrest and apoptosis.

Retaspimycin is a prodrug that is rapidly converted in vivo to the active HSP90 inhibitor tanespimycin (17-AAG). The prodrug design improves aqueous solubility relative to 17-AAG and enables intravenous administration, facilitating systemic delivery in clinical settings. Its intended clinical use is as an anticancer agent, either as monotherapy or in combination with chemotherapy or other targeted therapies.

In clinical development, retaspimycin was evaluated in Phase I and II trials across several solid tumors and hematologic malignancies, frequently in combination regimens. While some studies reported signs of antitumor activity, the program did not advance to regulatory approval, and no approved indications exist in major markets. Research into HSP90 inhibitors continues with other agents, reflecting ongoing interest in targeting this chaperone's broad network of client proteins.

See also: tanespimycin, 17-AAG, HSP90 inhibitors.