An engineered dimeric fragment of hepatocyte growth factor is a potent c‐MET agonist.

Hepatocyte growth factor (HGF), through activation of the c‐MET receptor, mediates biological processes critical for tissue regeneration; however, its clinical application is limited by protein instability and poor recombinant expression. We previously engineered an HGF fragment (eNK1) that possesses increased stability and expression yield and developed a c‐MET agonist by coupling eNK1 through an introduced cysteine residue. Here, we further characterize this eNK1 dimer and show it elicits significantly greater c‐MET activation, cell migration, and proliferation than the eNK1 monomer. The efficacy of the eNK1 dimer was similar to HGF, suggesting its promise as a c‐MET agonist.HGF is difficult to produce and unstable, highlighting a need for c‐MET agonists. A disulfide‐linked dimer (eNK1 dimer) was created from an engineered HGF fragment. The eNK1 monomer is a weak agonist and only activates c‐MET at high concentrations. The eNK1 dimer is a potent activator of c‐MET, cell migration, and proliferation. The eNK1 dimer elicits similar biological activity compared to HGF. [ABSTRACT FROM AUTHOR]