4HVG

JAK3 kinase domain in complex with 2-Cyclopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((S)-2-hydroxy-1,2-dimethyl-propyl)-amide

4HVG の概要

• エントリーDOI: 10.2210/pdb4hvg/pdb
• 関連するPDBエントリー: 4HVD 4HVH 4HVI
• 分子名称: Tyrosine-protein kinase JAK3, 2-cyclopropyl-N-[(2S)-3-hydroxy-3-methylbutan-2-yl]-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (3 entities in total)
• 機能のキーワード: kinase-inhibitor complex, 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 (By similarity): P52333
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35901.94

構造登録者

Kuglstatter, A.,Shao, A. (登録日: 2012-11-06, 公開日: 2013-01-16, 最終更新日: 2023-09-20)

主引用文献

Soth, M.,Hermann, J.C.,Yee, C.,Alam, M.,Barnett, J.W.,Berry, P.,Browner, M.F.,Frank, K.,Frauchiger, S.,Harris, S.,He, Y.,Hekmat-Nejad, M.,Hendricks, T.,Henningsen, R.,Hilgenkamp, R.,Ho, H.,Hoffman, A.,Hsu, P.Y.,Hu, D.Q.,Itano, A.,Jaime-Figueroa, S.,Jahangir, A.,Jin, S.,Kuglstatter, A.,Kutach, A.K.,Liao, C.,Lynch, S.,Menke, J.,Niu, L.,Patel, V.,Railkar, A.,Roy, D.,Shao, A.,Shaw, D.,Steiner, S.,Sun, Y.,Tan, S.L.,Wang, S.,Vu, M.D.
3-Amido Pyrrolopyrazine JAK Kinase Inhibitors: Development of a JAK3 vs JAK1 Selective Inhibitor and Evaluation in Cellular and in Vivo Models.
J.Med.Chem., 56:345-356, 2013

PubMed Abstract: The Janus kinases (JAKs) are involved in multiple signaling networks relevant to inflammatory diseases, and inhibition of one or more members of this class may modulate disease activity or progression. We optimized a new inhibitor scaffold, 3-amido-5-cyclopropylpyrrolopyrazines, to a potent example with reasonable kinome selectivity, including selectivity for JAK3 versus JAK1, and good biopharmaceutical properties. Evaluation of this analogue in cellular and in vivo models confirmed functional selectivity for modulation of a JAK3/JAK1-dependent IL-2 stimulated pathway over a JAK1/JAK2/Tyk2-dependent IL-6 stimulated pathway.

PubMed: 23214979
DOI: 10.1021/jm301646k

実験手法

X-RAY DIFFRACTION (2.75 Å)