AW054

AW054 is a methotrexate-based albumin-binding prodrug designed for targeted delivery to solid tumors. It consists of a methotrexate moiety linked to a 6-maleimidocaproic acid (EMC) group via a cathepsin B-cleavable peptide spacer (D-Ala-Phe-Lys-Lys). Upon intravenous administration, the maleimide group reacts rapidly and selectively with the Cysteine-34 thiol group of endogenous serum albumin. This conjugation allows the drug to exploit the long half-life of albumin and its preferential accumulation in tumor tissues through the enhanced permeability and retention (EPR) effect. Within the tumor microenvironment or after endocytosis, lysosomal proteases like cathepsin B cleave the peptide linker, releasing the active cytotoxic agent, methotrexate. Methotrexate then exerts its effect by inhibiting dihydrofolate reductase, thereby disrupting DNA synthesis and cell proliferation. AW054 has been evaluated in preclinical studies, particularly in pancreatic carcinoma models, often as part of combination regimens with other albumin-binding prodrugs like DOXO-EMCH.

Other names

EMC-D-Ala-Phe-Lys-Lys(gamma-MTX)-OH6-maleimidocaproyl-D-alanyl-phenylalanyl-lysyl-lysyl(gamma-methotrexate)