PDBsum entry 4knb

Transferase

PDB id: 4knb

Contents

Protein chains

273 a.a.

256 a.a.

271 a.a.

247 a.a.

Ligands

1RU ×4

GBL ×3

Waters ×78

PDB id:

4knb

Name:

Transferase

Title:

C-met in complex with osi ligand

Structure:

Hepatocyte growth factor receptor. Chain: a, b, c, d. Fragment: protein kinase domain (unp residues 1060-1346). Synonym: hgf receptor, hgf/sf receptor, proto-oncogenE C-met, scatter factor receptor, sf receptor, tyrosine-protein kinase met. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: met. Expressed in: insecta. Expression_system_taxid: 50557.

Resolution:

2.40Å R-factor: 0.241 R-free: 0.288

Authors:

J.Wang,A.G.Steinig,A.H.Li,X.Chen,H.Dong,C.Ferraro,M.Jin,M.Kadalbajoo, A.Kleinberg,K.M.Stolz,P.A.Tavares-Greco,T.Wang,M.R.Albertella, Y.Peng,L.Crew,J.Kahler

Key ref:

A.G.Steinig et al. (2013). Novel 6-aminofuro[3,2-c]pyridines as potent, orally efficacious inhibitors of cMET and RON kinases. Bioorg Med Chem Lett, 23, 4381-4387. PubMed id: 23773865 DOI: 10.1016/j.bmcl.2013.05.074

Date:

09-May-13 Release date: 30-Apr-14

Protein chain

P08581  (MET_HUMAN) -  Hepatocyte growth factor receptor from Homo sapiens

Seq: 1390 a.a.

Struc: 273 a.a.

Protein chain

P08581  (MET_HUMAN) -  Hepatocyte growth factor receptor from Homo sapiens

Seq: 1390 a.a.

Struc: 256 a.a.

Protein chain

P08581  (MET_HUMAN) -  Hepatocyte growth factor receptor from Homo sapiens

Seq: 1390 a.a.

Struc: 271 a.a.

Protein chain

P08581  (MET_HUMAN) -  Hepatocyte growth factor receptor from Homo sapiens

Seq: 1390 a.a.

Struc: 247 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D: E.C.2.7.10.1 - receptor protein-tyrosine kinase.
• Reaction: L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.bmcl.2013.05.074

Bioorg Med Chem Lett 23:4381-4387 (2013)

PubMed id: 23773865

Novel 6-aminofuro[3,2-c]pyridines as potent, orally efficacious inhibitors of cMET and RON kinases.

A.G.Steinig, A.H.Li, J.Wang, X.Chen, H.Dong, C.Ferraro, M.Jin, M.Kadalbajoo, A.Kleinberg, K.M.Stolz, P.A.Tavares-Greco, T.Wang, M.R.Albertella, Y.Peng, L.Crew, J.Kahler, J.Kan, R.Schulz, A.Cooke, M.Bittner, R.W.Turton, M.Franklin, P.Gokhale, D.Landfair, C.Mantis, J.Workman, R.Wild, J.Pachter, D.Epstein, M.J.Mulvihill.

ABSTRACT

A series of novel 6-aminofuro[3,2-c]pyridines as kinase inhibitors is described, most notably, OSI-296 (6). We discuss our exploration of structure-activity relationships and optimization leading to OSI-296 and disclose its pharmacological activity against cMET and RON in cellular assays. OSI-296 is a potent and selective inhibitor of cMET and RON kinases that shows in vivo efficacy in tumor xenografts models upon oral dosing and is well tolerated.