fibroblast activation protein alpha-activated doxorubicin prodrug AVA6000

A prodrug of the anthracycline antineoplastic antibiotic doxorubicin composed of doxorubicin covalently bonded to the dipeptide N-(pyridine-4-carbonyl)-D-Ala-L-Pro, with potential antineoplastic activity. Upon administration, fibroblast activation protein alpha (FAP)-activated doxorubicin prodrug AVA6000 is hydrolyzed by FAP, which is overexpressed on cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME). Doxorubicin is released in the TME, and intercalates into DNA and interacts with topoisomerase II. This leads to an inhibition of DNA replication and repair, and prevents RNA and protein synthesis. By targeting the delivery of doxorubicin directly to the tumor, AVA6000 may result in less systemic toxicities. FAP, a membrane-bound protease, is overexpressed on CAFs in various tumors but minimally expressed on normal, healthy cells.