GENTAUR Belgium BVBA BE0473327336 Voortstraat 49, 1910 Kampenhout BELGIUM Tel 0032 16 58 90 45
GENTAUR U.S.A Genprice Inc,Logistics 547 Yurok Circle, SanJose, CA 95123
Tel (408) 780-0908, Fax (408) 780-0908, [email protected]

Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, Gentaur another in time delivery

Pubmed ID: 34902246
Publication Date: 2021/12/13

Macrocyclic Inhibitors of HGF-Activating Serine Proteases Overcome Resistance to Receptor Tyrosine Kinase Inhibitors and Block Lung Cancer Progression.

Hepatocyte growth factor (HGF), the ligand for the MET receptor tyrosine kinase, is a tumor-promoting factor that is abundant in the tumor microenvironment. Proteolytic activation of inactive pro-HGF by one or more of the serine endopeptidases matriptase, hepsin, and HGF activator is the rate-limiting step in HGF/MET signaling. Herein, we have rationally designed a novel class of side chain cyclized macrocyclic peptide inhibitors. The new series of cyclic tripeptides has superior metabolic stability and significantly improved pharmacokinetics in mice relative to the corresponding linear peptides. We identified the lead compound VD2173 that potently inhibits matriptase and hepsin, which was tested in parallel alongside the acyclic inhibitor ZFH7116 using both in vitro and in vivo models of lung cancer. We demonstrated that both compounds block pro-HGF activation, abrogate HGF-mediated wound healing, and overcome resistance to EGFR- and MET-targeted therapy in lung cancer models. Furthermore, VD2173 inhibited HGF-dependent growth of lung cancer tumors in mice.
Authors: Damalanka Vishnu C , Voss Jorine J L P , Mahoney Matthew W , Primeau Tina , Li Shunqiang , Klampfer Lidija , Janetka James W ,


  1. [Last access 2021/12/13].

Related products :

Catalog number Product name Quantity
ATGP2037 Proteases & Inhibitors: MRI, 1-157aa, Human, His tag, E.coli 100ug
ATGP2037 Proteases & Inhibitors: MRI, 1-157aa, Human, His tag, E.coli 20ug
ATGP0764 Proteases & Inhibitors: BLMH, 1-455aa, Human, His tag, E.coli 100ug
ATGP2040 Proteases & Inhibitors: CST3, 27-146aa, Human, His tag, E.coli 50ug
ATGP2117 Proteases & Inhibitors: CST11, 26-103aa, Human, His tag, E.coli 0.5mg