1Y6B
Crystal structure of VEGFR2 in complex with a 2-anilino-5-aryl-oxazole inhibitor
Summary for 1Y6B
| Entry DOI | 10.2210/pdb1y6b/pdb |
| Related | 1VR2 1Y6A |
| Descriptor | Vascular endothelial growth factor receptor 2, N-(CYCLOPROPYLMETHYL)-4-(METHYLOXY)-3-({5-[3-(3-PYRIDINYL)PHENYL]-1,3-OXAZOL-2-YL}AMINO)BENZENESULFONAMIDE (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 | 42153.24 |
| 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 Cited by 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: 15743202DOI: 10.1021/jm049538w PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
Download full validation report
