3CJG

Crystal structure of VEGFR2 in complex with a 3,4,5-trimethoxy aniline containing pyrimidine

Summary for 3CJG

• Entry DOI: 10.2210/pdb3cjg/pdb
• Related: 1VR2 1Y6A 1Y6B 1YWN 3CJF
• Descriptor: Vascular endothelial growth factor receptor 2, SULFATE ION, N~4~-methyl-N~4~-(3-methyl-1H-indazol-6-yl)-N~2~-(3,4,5-trimethoxyphenyl)pyrimidine-2,4-diamine, ... (4 entities in total)
• Functional Keywords: vascular endothelial growth factor receptor 2. vegfr-2, kinase insert domain receptor, protein-tyrosine kinase receptor flk-1, angiogenesis, atp-binding, developmental protein, differentiation, glycoprotein, host-virus interaction, immunoglobulin domain, membrane, nucleotide-binding, phosphoprotein, transferase, transmembrane, tyrosine-protein kinase
• Biological source: Homo sapiens (human); More
• 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: 36056.50

Authors

Nolte, R.T. (deposition date: 2008-03-12, release date: 2008-10-07, Last modification date: 2024-10-30)

Primary citation

Harris, P.A.,Boloor, A.,Cheung, M.,Kumar, R.,Crosby, R.M.,Davis-Ward, R.G.,Epperly, A.H.,Hinkle, K.W.,Hunter, R.N.,Johnson, J.H.,Knick, V.B.,Laudeman, C.P.,Luttrell, D.K.,Mook, R.A.,Nolte, R.T.,Rudolph, S.K.,Szewczyk, J.R.,Truesdale, A.T.,Veal, J.M.,Wang, L.,Stafford, J.A.
Discovery of 5-[[4-[(2,3-dimethyl-2H-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a novel and potent vascular endothelial growth factor receptor inhibitor.
J.Med.Chem., 51:4632-4640, 2008

PubMed Abstract: Inhibition of the vascular endothelial growth factor (VEGF) signaling pathway has emerged as one of the most promising new approaches for cancer therapy. We describe herein the key steps starting from an initial screening hit leading to the discovery of pazopanib, N(4)-(2,3-dimethyl-2H-indazol-6-yl)-N(4)-methyl-N(2)-(4-methyl-3-sulfonamidophenyl)-2,4-pyrimidinediamine, a potent pan-VEGF receptor (VEGFR) inhibitor under clinical development for renal-cell cancer and other solid tumors.

PubMed: 18620382
DOI: 10.1021/jm800566m

Experimental method

X-RAY DIFFRACTION (2.25 Å)