4RX9

SYK Catalytic Domain Complexed with a Potent Pyrimidine Inhibitor

Summary for 4RX9

Entry DOI	10.2210/pdb4rx9/pdb
Related	4RX7 4RX8
Descriptor	Tyrosine-protein kinase SYK, GLYCEROL, 2-{[(1R,2S)-2-aminocyclohexyl]amino}-4-{[3-(2H-1,2,3-triazol-2-yl)phenyl]amino}pyrimidine-5-carboxamide, ... (4 entities in total)
Functional Keywords	transferase-transferase inhibitor complex, transferase/transferase inhibitor
Biological source	Homo sapiens (human)
Cellular location	Cell membrane : P43405
Total number of polymer chains	1
Total formula weight	34293.45
Authors	Lee, C.C. (deposition date: 2014-12-09, release date: 2015-03-18, Last modification date: 2024-02-28)
Primary citation	Thoma, G.,Smith, A.B.,van Eis, M.J.,Vangrevelinghe, E.,Blanz, J.,Aichholz, R.,Littlewood-Evans, A.,Lee, C.C.,Liu, H.,Zerwes, H.G. Discovery and profiling of a selective and efficacious syk inhibitor. J.Med.Chem., 58:1950-1963, 2015 Cited by PubMed Abstract: We describe the discovery of selective and potent Syk inhibitor 11, which exhibited favorable PK profiles in rat and dog and was found to be active in a collagen-induced arthritis model in rats. Compound 11 was selected for further profiling, but, unfortunately, in GLP toxicological studies it showed liver findings in rat and dog. Nevertheless, 11 could become a valuable tool compound to investigate the rich biology of Syk in vitro and in vivo. PubMed: 25633741 DOI: 10.1021/jm5018863 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (1.75 Å)

Structure validation