7KXM

BTK1 SOAKED WITH COMPOUND 5, Y551 IS SEQUESTERED

7KXM の概要

• エントリーDOI: 10.2210/pdb7kxm/pdb
• 分子名称: Tyrosine-protein kinase BTK, 4-tert-butyl-N-(2-methyl-3-{2-[4-(morpholine-4-carbonyl)phenyl]-1H-imidazo[4,5-b]pyridin-7-yl}phenyl)benzamide (3 entities in total)
• 機能のキーワード: protein kinase, transferase
• 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: 32171.97

構造登録者

Gardberg, A. (登録日: 2020-12-04, 公開日: 2021-05-19, 最終更新日: 2023-10-18)

主引用文献

Qiu, H.,Ali, Z.,Bender, A.,Caldwell, R.,Chen, Y.Y.,Fang, Z.,Gardberg, A.,Glaser, N.,Goettsche, A.,Goutopoulos, A.,Grenningloh, R.,Hanschke, B.,Head, J.,Johnson, T.,Jones, C.,Jones, R.,Kulkarni, S.,Maurer, C.,Morandi, F.,Neagu, C.,Poetzsch, S.,Potnick, J.,Schmidt, R.,Roe, K.,Viacava Follis, A.,Wing, C.,Zhu, X.,Sherer, B.
Discovery of potent and selective reversible Bruton's tyrosine kinase inhibitors.
Bioorg.Med.Chem., 40:116163-116163, 2021

PubMed Abstract: Bruton's tyrosine kinase (BTK) is a cytoplasmic, non-receptor tyrosine kinase member of the TEC family of tyrosine kinases. Pre-clinical and clinical data have shown that targeting BTK can be used for the treatment for B-cell disorders. Here we disclose the discovery of a novel imidazo[4,5-b]pyridine series of potent, selective reversible BTK inhibitors through a rational design approach. From a starting hit molecule 1, medicinal chemistry optimization led to the development of a lead compound 30, which exhibited 58 nM BTK inhibitory potency in human whole blood and high kinome selectivity. Additionally, the compound demonstrated favorable pharmacokinetics (PK), and showed potent dose-dependent efficacy in a rat CIA model.

PubMed: 33932711
DOI: 10.1016/j.bmc.2021.116163

実験手法

X-RAY DIFFRACTION (1.33 Å)