5CY3

SYK catalytic domain complexed with a potent and orally bioavailable benzisothiazole inhibitor

Summary for 5CY3

Entry DOI	10.2210/pdb5cy3/pdb
Related	5CXH
Descriptor	Tyrosine-protein kinase SYK, (5R)-5-[(1R)-1-{[6-(1-methyl-1H-pyrazol-4-yl)-2,1-benzothiazol-4-yl]oxy}ethyl]-1,3-oxazolidin-2-one (3 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	34200.32
Authors	Lee, C.C. (deposition date: 2015-07-30, release date: 2015-09-23, Last modification date: 2024-03-06)
Primary citation	Thoma, G.,Veenstra, S.,Strang, R.,Blanz, J.,Vangrevelinghe, E.,Berghausen, J.,Lee, C.C.,Zerwes, H.G. Orally bioavailable Syk inhibitors with activity in a rat PK/PD model. Bioorg.Med.Chem.Lett., 25:4642-4647, 2015 Cited by PubMed Abstract: Design and optimization of benzo- and pyrido-thiazoles/isothiazoles are reported leading to the discovery of the potent, orally bioavailable Syk inhibitor 5, which was found to be active in a rat PK/PD model. Compound 5 showed acceptable overall kinase selectivity. However, in addition to Syk it also inhibited Aurora kinase in enzymatic and cellular settings leading to findings in the micronucleus assay. As a consequence, compound 5 was not further pursued. PubMed: 26320624 DOI: 10.1016/j.bmcl.2015.08.037 PDB entries with the same primary citation
Experimental method	X-RAY DIFFRACTION (1.76 Å)

Structure validation