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: 26712116
Publication Date: 2015/12/28

Developing Antagonists for the Met-HGF/SF Protein-Protein Interaction Using a Fragment-Based Approach.

In many cancers, aberrant activation of the Met receptor tyrosine kinase leads to dissociation of cells from the primary tumor, causing metastasis. Accordingly, Met is a high-profile target for the development of cancer therapies, and progress has been made through development of small molecule kinase inhibitors and antibodies. However, both approaches pose significant challenges with respect to either target specificity (kinase inhibitors) or the cost involved in treating large patient cohorts (antibodies). Here, we use a fragment-based approach in order to target the protein-protein interaction (PPI) between the α-chain of hepatocyte growth factor/scatter factor (HGF/SF; the NK1 fragment) and its high-affinity binding site located on the Met Sema domain. Surface plasmon resonance was used for initial fragment library screening and hits were developed into larger compounds using substructure (similarity) searches. We identified compounds able to interfere with NK1 binding to Met, disrupt Met signaling, and inhibit tumorsphere generation and cell migration. Using molecular docking, we concluded that some of these compounds inhibit the PPI directly, whereas others act indirectly. Our results indicate that chemical fragments can efficiently target the HGF/SF-Met interface and may be used as building blocks for generating biologically active lead compounds. This strategy may have broad application for the development of a new class of Met inhibitors, namely receptor antagonists, and in general for the development of small molecule PPI inhibitors of key therapeutic targets when structural information is not available.
Authors: Winter Anja , Sigurdardottir Anna G , DiCara Danielle , Valenti Giovanni , Blundell Tom L , Gherardi Ermanno ,


  1. [Last access 2015/12/28].

Related products :

Catalog number Product name Quantity
PAH-G1-2 Protein Arrays containing 234 Human Protein for simultaneous detection of Protein function, including Protein-protein interaction, Protein modification, antibody specificity, auto-antibody and small m 1 glass slide with 2 sub-arrays
28-200 ZNF22 encodes a protein that is expressed in the epithelial component of the developing tooth organ during early bud and cap stages as well as in osteoblasts of craniofacial bone and the developing to 0.1 mg
EIAAB40512 Mouse,Mus musculus,Phosphoserine_threonine_tyrosine interaction protein,Protein tyrosine phosphatase-like protein,Serine_threonine_tyrosine-interacting protein,Styx
30-187 PSAT1 is likely a phosphoserine aminotransferase, based on similarity to proteins in mouse, rabbit, and Drosophila.The protein encoded by this gene is likely a phosphoserine aminotransferase, based on 0.05 mg
EIAAB44595 Glutaminase-interacting protein 3,Homo sapiens,Human,Tax interaction protein 1,Tax1-binding protein 3,TAX1BP3,TIP1,TIP-1