Dipeptidyl peptidase 4, Dipeptidyl peptidase 8, Dipeptidyl peptidase 9, Fibroblast activation protein alpha (DPP4, DPP8, DPP9, FAP)

This entry represents a grouping of four distinct but related serine protease enzymes: Dipeptidyl peptidase 4 (DPP4), Dipeptidyl peptidase 8 (DPP8), Dipeptidyl peptidase 9 (DPP9), and Fibroblast activation protein, alpha (FAP). While each is an individual therapeutic target with roles in metabolism, immunity, and tissue remodeling, considering them as a single canonical target is incorrect. They share common molecular classifications as serine exopeptidases of the DPP4 activity and structure homolog (DASH) family but possess distinct biological functions, disease associations, and therapeutic implications. DPP4 is a well-established target for type 2 diabetes. DPP8 and DPP9 are intracellular enzymes with significant safety concerns due to immune-related toxicities upon inhibition. FAP is a membrane-bound enzyme targeted in cancer and fibrotic diseases. Their mechanisms of action and safety profiles differ considerably, necessitating individual targeting strategies.

Other names

DPPIVCD26Adenosine deaminase complexing protein 2DPP-8DPP-9FAPASeprase

These enzymes, members of the DPP4 activity and structure homolog (DASH) family, are involved in cleaving dipeptides. Their specific mechanisms of action vary: DPP4 inhibition prevents degradation of incretin hormones, enhancing insulin secretion; DPP8/9 inhibition leads to immune cell pyroptosis and alters intracellular peptide turnover; FAP inhibition/payload delivery affects tumor microenvironment and fibrosis. Considering them as a single target's mechanism is inaccurate due to their distinct biological contexts and outcomes.