4PX6

SYK catalytic domain in complex with a potent pyridopyrimidinone inhibitor

Summary for 4PX6

• Entry DOI: 10.2210/pdb4px6/pdb
• Descriptor: Tyrosine-protein kinase SYK, 7-{[(1R,2S)-2-aminocyclohexyl]amino}-5-(1H-indol-7-ylamino)pyrido[4,3-d]pyrimidin-4(3H)-one (3 entities in total)
• Functional Keywords: kinase domain, phosphotransferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane (Probable): P43405
• Total number of polymer chains: 1
• Total formula weight: 34245.38

Authors

Lee, C.C. (deposition date: 2014-03-21, release date: 2014-04-23, Last modification date: 2023-09-20)

Primary citation

Thoma, G.,Blanz, J.,Buhlmayer, P.,Druckes, P.,Kittelmann, M.,Smith, A.B.,van Eis, M.,Vangrevelinghe, E.,Zerwes, H.G.,Che, J.J.,He, X.,Jin, Y.,Lee, C.C.,Michellys, P.Y.,Uno, T.,Liu, H.
Syk inhibitors with high potency in presence of blood.
Bioorg.Med.Chem.Lett., 24:2278-2282, 2014

PubMed Abstract: We describe two series of Syk inhibitors which potently abrogate Syk kinase function in enzymatic assays, cellular assays and in primary cells in the presence of blood. Introduction of a 7-aminoindole substituent led to derivatives with good kinase selectivity and little or no hERG channel inhibition (3b, 10c).

PubMed: 24726806
DOI: 10.1016/j.bmcl.2014.03.075

Experimental method

X-RAY DIFFRACTION (1.6 Å)