4YJP

THE KINASE DOMAIN OF HUMAN SPLEEN TYROSINE (SYK) IN COMPLEX WITH GTC000223

Summary for 4YJP

• Entry DOI: 10.2210/pdb4yjp/pdb
• Descriptor: Tyrosine-protein kinase SYK, 2-[{2-[(1,1-dioxido-2,3-dihydro-1,2-benzothiazol-6-yl)amino]pyrimidin-4-yl}(1H-indazol-4-yl)amino]ethanol, DIMETHYL SULFOXIDE, ... (4 entities in total)
• Functional Keywords: syk, non-receptor tyrosine kinase, spleen tyrosine kinase, transferase, phosphorylation, transferase-transferase inhibitor complex
• Biological source: Homo sapiens (Human)
• Cellular location: Cell membrane : P43405
• Total number of polymer chains: 1
• Total formula weight: 33166.26

Authors

Somers, D.O.,Neu, M. (deposition date: 2015-03-03, release date: 2015-09-30, Last modification date: 2024-05-01)

Primary citation

Liddle, J.,Atkinson, F.L.,Barker, M.D.,Carter, P.S.,Curtis, N.R.,Davis, R.P.,Douault, C.,Dickson, M.C.,Elwes, D.,Garton, N.S.,Gray, M.,Hayhow, T.G.,Hobbs, C.I.,Jones, E.,Leach, S.,Leavens, K.,Lewis, H.D.,McCleary, S.,Neu, M.,Patel, V.K.,Preston, A.G.,Ramirez-Molina, C.,Shipley, T.J.,Skone, P.A.,Smithers, N.,Somers, D.O.,Walker, A.L.,Watson, R.J.,Weingarten, G.G.
Discovery of GSK143, a highly potent, selective and orally efficacious spleen tyrosine kinase inhibitor.
Bioorg. Med. Chem. Lett., 21:6188-6194, 2011

PubMed Abstract: The lead optimisation of the diaminopyrimidine carboxamide series of spleen tyrosine kinase inhibitors is described. The medicinal chemistry strategy was focused on optimising the human whole blood activity whilst achieving a sufficient margin over liability kinases and hERG activity. GSK143 is a potent and highly selective SYK inhibitor showing good efficacy in the rat Arthus model.

PubMed: 21903390
DOI: 10.1016/j.bmcl.2011.07.082

Experimental method

X-RAY DIFFRACTION (1.83 Å)