VD2173

VD2173 is a rationally designed, side-chain cyclized macrocyclic tripeptide inhibitor that targets HGF-activating serine proteases, specifically matriptase and hepsin. By blocking the proteolytic activation of inactive pro-HGF into its active form, VD2173 inhibits HGF/MET signaling, a key pathway in tumor progression and resistance to therapy. In preclinical models of lung cancer, VD2173 has demonstrated the ability to abrogate HGF-mediated wound healing, overcome resistance to EGFR- and MET-targeted therapies, and inhibit HGF-dependent tumor growth. It exhibits superior metabolic stability and significantly improved pharmacokinetics compared to its linear peptide counterparts.