4K77

JAK1 kinase (JH1 domain) in complex with compound 6

Summary for 4K77

• Entry DOI: 10.2210/pdb4k77/pdb
• Descriptor: Tyrosine-protein kinase JAK1, 4-(cyclohexylamino)pyrido[3,4-d]pyrimidin-8(7H)-one (3 entities in total)
• Functional Keywords: protein kinase, phosphotransfer, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Endomembrane system; Peripheral membrane protein: P23458
• Total number of polymer chains: 2
• Total formula weight: 69981.77

Authors

Eigenbrot, C.,Shia, S. (deposition date: 2013-04-16, release date: 2013-10-02, Last modification date: 2024-11-20)

Primary citation

Labadie, S.,Barrett, K.,Blair, W.S.,Chang, C.,Deshmukh, G.,Eigenbrot, C.,Gibbons, P.,Johnson, A.,Kenny, J.R.,Kohli, P.B.,Liimatta, M.,Lupardus, P.J.,Shia, S.,Steffek, M.,Ubhayakar, S.,Abbema, A.V.,Zak, M.
Design and evaluation of novel 8-oxo-pyridopyrimidine Jak1/2 inhibitors.
Bioorg.Med.Chem.Lett., 23:5923-5930, 2013

PubMed Abstract: A highly ligand efficient, novel 8-oxo-pyridopyrimidine containing inhibitor of Jak1 and Jak2 isoforms with a pyridone moiety as the hinge-binding motif was discovered. Structure-based design strategies were applied to significantly improve enzyme potency and the polarity of the molecule was adjusted to gain cellular activity. The crystal structures of two representative inhibitors bound to Jak1 were obtained to enable SAR exploration.

PubMed: 24042009
DOI: 10.1016/j.bmcl.2013.08.082

Experimental method

X-RAY DIFFRACTION (2.4 Å)