zosuquidar albumin prodrug

Zosuquidar albumin prodrug is an experimental, acid-sensitive, albumin-binding prodrug of the third-generation P-glycoprotein (P-gp) inhibitor zosuquidar (LY335979). Developed in an academic research setting at the Tumor Biology Center in Freiburg, Germany, the prodrug is synthesized using a maleimide hydrazone linker system that introduces acetylbenzoic acid at the hydroxyl group of zosuquidar, followed by derivatization with 6-maleimidocaproyl hydrazide. Upon intravenous administration, the maleimide group binds rapidly and selectively to the cysteine-34 position of endogenous serum albumin, utilizing albumin as a macromolecular carrier to improve tumor targeting and reduce systemic toxicity. In acidic tumor microenvironments (pH ~5.0), the hydrazone bond is cleaved, releasing the active zosuquidar derivative. The prodrug is designed to reverse multidrug resistance (MDR) in breast cancer and other malignancies by inhibiting P-gp-mediated drug efflux, thereby re-sensitizing resistant tumor cells to chemotherapeutic agents such as doxorubicin.

Other names

acid-sensitive albumin-binding prodrug of zosuquidarzosuquidar prodrugzosuquidar-albumin conjugate