HGF-inhibitory macrocyclic peptide -- mechanisms and potential cancer theranostics

(Kanazawa University) Hepatocyte growth factor (HGF) is involved in cancer progression through MET receptor signaling. Here, HiP-8, a 12 amino-acid macrocyclic peptide, was identified to selectively recognize active HGF. Biochemical analysis and high-speed AFM demonstrated HiP-8 restricted dynamic domains of HGF, resulting in allosteric inhibition. Positron emission tomography using radiotracer HiP-8 enabled noninvasive visualization and inhibition of HGF-MET activation status in tumors in mouse...