4KNB

C-Met in complex with OSI ligand

PDB DOI: https://doi.org/10.2210/pdb4KNB/pdb

Classification: TRANSFERASE
Organism(s): Homo sapiens
Expression System: Insecta
Mutation(s): No

Deposited: 2013-05-09 Released: 2014-04-30
Deposition Author(s): Wang, J., Steinig, A.G., Li, A.H., Chen, X., Dong, H., Ferraro, C., Jin, M., Kadalbajoo, M., Kleinberg, A., Stolz, K.M., Tavares-Greco, P.A., Wang, T., Albertella, M.R., Peng, Y., Crew, L., Kahler, J.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.40 ?
R-Value Free: 0.288
R-Value Work: 0.240
R-Value Observed: 0.241

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

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

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

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

PubMed: 23773865 Search on PubMed
DOI: https://doi.org/10.1016/j.bmcl.2013.05.074
Primary Citation of Related Structures:
4KNB

PubMed 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.

Organizational Affiliation

OSI Pharmaceuticals, LLC, A Wholly-Owned Subsidiary of Astellas US, 1 Bioscience Park Drive, Farmingdale, NY 11735, USA. arnosteinig@gmail.com

Macromolecule Content

Total Structure Weight: 132.42 kDa
Atom Count: 8,611
Modelled Residue Count: 1,047
Deposited Residue Count: 1,148
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Hepatocyte growth factor receptor	A, B, C, D	287	Homo sapiens	Mutation(s): 0 Gene Names: MET EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P08581 (Homo sapiens) Explore P08581 Go to UniProtKB: P08581
PHAROS: P08581 GTEx: ENSG00000105976
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	P08581
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 2 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
1RU Query on 1RU Download Ideal Coordinates CCD File SDF format, chain E [auth A] SDF format, chain H [auth B] SDF format, chain J [auth C] SDF format, chain K [auth D] MOL2 format, chain E [auth A] MOL2 format, chain H [auth B] MOL2 format, chain J [auth C] MOL2 format, chain K [auth D] mmCIF format, chain E [auth A] mmCIF format, chain H [auth B] mmCIF format, chain J [auth C] mmCIF format, chain K [auth D]	E [auth A], H [auth B], J [auth C], K [auth D]	7-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-[1-(piperidin-4-yl)-1H-pyrazol-4-yl]furo[3,2-c]pyridin-6-amine C₂₃ H₂₂ Cl₂ F N₅ O₂ RFKWZWJQRQCLJF-GFCCVEGCSA-N		Interactions Focus chain E [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain K [auth D] Interactions & Density Focus chain E [auth A] Focus chain H [auth B] Focus chain J [auth C] Focus chain K [auth D]
GBL Query on GBL Download Ideal Coordinates CCD File SDF format, chain F [auth A] SDF format, chain G [auth A] SDF format, chain I [auth B] MOL2 format, chain F [auth A] MOL2 format, chain G [auth A] MOL2 format, chain I [auth B] mmCIF format, chain F [auth A] mmCIF format, chain G [auth A] mmCIF format, chain I [auth B]	F [auth A], G [auth A], I [auth B]	GAMMA-BUTYROLACTONE C₄ H₆ O₂ YEJRWHAVMIAJKC-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Focus chain G [auth A] Focus chain I [auth B] Interactions & Density Focus chain F [auth A] Focus chain G [auth A] Focus chain I [auth B]