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3M NK1 is an engineered recombinant protein antagonist of the Met receptor (hepatocyte growth factor receptor). It is a triple-mutant version of NK1, a naturally occurring truncated isoform of hepatocyte growth factor (HGF) that consists of the N-terminal (N) and first kringle (K1) domains. The molecule contains three specific charge-reversal mutations (K60, K62, and R73) in the N domain designed to disrupt binding to cell surface heparan sulfate (HS) glycans while maintaining high-affinity binding to the Met receptor. Because HS binding is essential for HGF-induced receptor dimerization and downstream signaling, 3M NK1 acts as a potent competitive inhibitor of both wild-type NK1 and full-length HGF. Preclinical studies have demonstrated that 3M NK1 can significantly impair the growth of HGF-dependent tumors, such as glioblastoma, by antagonizing autocrine and paracrine HGF/Met signaling pathways.
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