6VNS

Crystal structure of TYK2 kinase with compound 13

6VNS の概要

• エントリーDOI: 10.2210/pdb6vns/pdb
• 分子名称: Non-receptor tyrosine-protein kinase TYK2, (1R,2R)-2-cyano-N-[(1S,5R)-3-(5-fluoro-2-{[1-(2-hydroxyethyl)-1H-pyrazol-4-yl]amino}pyrimidin-4-yl)-3-azabicyclo[3.1.0]hexan-1-yl]cyclopropane-1-carboxamide (3 entities in total)
• 機能のキーワード: kinase, transferase, transferase-inhibitor complex, transferase/inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36962.99

構造登録者

Vajdos, F.F. (登録日: 2020-01-29, 公開日: 2020-04-08, 最終更新日: 2024-11-20)

主引用文献

Fensome, A.,Ambler, C.M.,Arnold, E.,Banker, M.E.,Clark, J.D.,Dowty, M.E.,Efremov, I.V.,Flick, A.,Gerstenberger, B.S.,Gifford, R.S.,Gopalsamy, A.,Hegen, M.,Jussif, J.,Limburg, D.C.,Lin, T.H.,Pierce, B.S.,Sharma, R.,Trujillo, J.I.,Vajdos, F.F.,Vincent, F.,Wan, Z.K.,Xing, L.,Yang, X.,Yang, X.
Design and optimization of a series of 4-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-2-amines: Dual inhibitors of TYK2 and JAK1.
Bioorg.Med.Chem., 28:115481-115481, 2020

PubMed Abstract: Herein, we disclose a new series of TYK2/ JAK1 inhibitors based upon a 3.1.0 azabicyclic substituted pyrimidine scaffold. We illustrate the use of structure-based drug design for the initial design and subsequent optimization of this series of compounds. One advanced example 19 met program objectives for potency, selectivity and ADME, and demonstrated oral activity in the adjuvant-induced arthritis rat model.

PubMed: 32253095
DOI: 10.1016/j.bmc.2020.115481

実験手法

X-RAY DIFFRACTION (2.09 Å)