4K77

JAK1 kinase (JH1 domain) in complex with compound 6

4K77 の概要

• エントリーDOI: 10.2210/pdb4k77/pdb
• 分子名称: Tyrosine-protein kinase JAK1, 4-(cyclohexylamino)pyrido[3,4-d]pyrimidin-8(7H)-one (3 entities in total)
• 機能のキーワード: protein kinase, phosphotransfer, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Endomembrane system; Peripheral membrane protein: P23458
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 69981.77

構造登録者

Eigenbrot, C.,Shia, S. (登録日: 2013-04-16, 公開日: 2013-10-02, 最終更新日: 2023-12-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)