4DEH

Crystal structure of c-Met in complex with triazolopyridinone inhibitor 3

Summary for 4DEH

• Entry DOI: 10.2210/pdb4deh/pdb
• Related: 4DEI 4DEg
• Descriptor: Hepatocyte growth factor receptor, 5-phenyl-3-(quinolin-6-ylmethyl)-3,5,6,7-tetrahydro-4H-[1,2,3]triazolo[4,5-c]pyridin-4-one (3 entities in total)
• Functional Keywords: proto-oncogene, receptor tyrosine kinase, rtk, atp-binding, hepatocyte growth factor/scatter factor, hgf/sf, phosphoprotein, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Membrane; Single-pass type I membrane protein. Isoform 3: Secreted: P08581
• Total number of polymer chains: 1
• Total formula weight: 35571.11

Authors

Whittington, D.A.,Bellon, S.F.,Long, A.M. (deposition date: 2012-01-20, release date: 2012-05-30, Last modification date: 2024-02-28)

Primary citation

Bode, C.M.,Boezio, A.A.,Albrecht, B.K.,Bellon, S.F.,Berry, L.,Broome, M.A.,Choquette, D.,Dussault, I.,Lewis, R.T.,Lin, M.H.,Rex, K.,Whittington, D.A.,Yang, Y.,Harmange, J.C.
Discovery and optimization of a potent and selective triazolopyridinone series of c-Met inhibitors.
Bioorg.Med.Chem.Lett., 22:4089-4093, 2012

PubMed Abstract: Deregulation of the receptor tyrosine kinase c-Met has been implicated in several human cancers and is an attractive target for small molecule drug discovery. Herein, we report the discovery of a structurally diverse series of carbon-linked quinoline triazolopyridinones, which demonstrates nanomolar inhibition of c-Met kinase activity. This novel series of inhibitors exhibits favorable pharmacokinetics as well as potent inhibition of HGF-mediated c-Met phosphorylation in a mouse liver pharmacodynamic model.

PubMed: 22595176
DOI: 10.1016/j.bmcl.2012.04.072

Experimental method

X-RAY DIFFRACTION (2 Å)