FAP-Exd-MMAE

FAP-Exd-MMAE is an experimental peptide-drug conjugate (PDC) designed to target tumors that express the glucagon-like peptide-1 receptor (GLP-1R), such as certain pancreatic cancers, medullary thyroid cancers, and insulinomas. The molecule consists of an exendin-4 derivative (a GLP-1R agonist) linked to the potent cytotoxic agent monomethyl auristatin E (MMAE). To minimize systemic toxicity and off-target effects on healthy GLP-1R-expressing tissues like the pancreas, the conjugate is engineered as a prodrug that remains inactive until it reaches the tumor microenvironment. Activation is triggered by fibroblast activation protein-alpha (FAP), a protease highly overexpressed in the reactive stroma of many solid tumors. Upon cleavage by FAP, the active exendin-4-MMAE moiety is released, allowing it to bind to GLP-1R on tumor cells, undergo internalization, and induce cell death via tubulin inhibition.

Other names

FAP-activated Exendin-4-MMAEFAP-Exd + monomethyl auristatin EFAP-Exd + MMAE