1Y6A

Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor

Summary for 1Y6A

• Entry DOI: 10.2210/pdb1y6a/pdb
• Related: 1Y6B 1vr2
• Descriptor: Vascular endothelial growth factor receptor 2, N-[5-(ETHYLSULFONYL)-2-METHOXYPHENYL]-5-[3-(2-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-AMINE (3 entities in total)
• Functional Keywords: transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cell junction . Isoform 1: Cell membrane; Single-pass type I membrane protein. Isoform 2: Secreted . Isoform 3: Secreted: P35968
• Total number of polymer chains: 1
• Total formula weight: 42112.19

Authors

Harris, P.A.,Cheung, M.,Hunter, R.N.,Brown, M.L.,Veal, J.M.,Nolte, R.T.,Wang, L.,Liu, W.,Crosby, R.M.,Johnson, J.H.,Epperly, A.H.,Kumar, R.,Luttrell, D.K.,Stafford, J.A. (deposition date: 2004-12-05, release date: 2005-06-07, Last modification date: 2024-02-14)

Primary citation

Harris, P.A.,Cheung, M.,Hunter, R.N.,Brown, M.L.,Veal, J.M.,Nolte, R.T.,Wang, L.,Liu, W.,Crosby, R.M.,Johnson, J.H.,Epperly, A.H.,Kumar, R.,Luttrell, D.K.,Stafford, J.A.
Discovery and evaluation of 2-anilino-5-aryloxazoles as a novel class of VEGFR2 kinase inhibitors.
J.Med.Chem., 48:1610-1619, 2005

PubMed Abstract: A series of derivatives of 2-anilino-5-phenyloxazole (5) has been identified as inhibitors of VEGFR2 kinase. Herein we describe the structure-activity relationship (SAR) of this novel template. Optimization of both aryl rings led to very potent inhibitors at both the enzymatic and cellular levels. Oxazole 39 had excellent solubility and good oral PK when dosed as the bis-mesylate salt and demonstrated moderate in vivo efficacy against HT29 human colon tumor xenografts. X-ray crystallography confirmed the proposed binding mode, and comparison of oxazoles 39 and 46 revealed interesting differences in orientation of 2-pyridyl and 3-pyridyl rings, respectively, attached at the meta position of the 5-phenyl ring.

PubMed: 15743202
DOI: 10.1021/jm049538w

Experimental method

X-RAY DIFFRACTION (2.1 Å)