5T1T

Irak4 kinase - compound 1 co-structure

5T1T の概要

• エントリーDOI: 10.2210/pdb5t1t/pdb
• 関連するPDBエントリー: 5T1S
• 分子名称: Interleukin-1 receptor-associated kinase 4, ~{N},~{N}-dimethyl-4-(6-nitroquinazolin-4-yl)oxy-cyclohexan-1-amine (3 entities in total)
• 機能のキーワード: inase, phosphatase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : Q9NWZ3
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 137090.20

構造登録者

Fischmann, T.O. (登録日: 2016-08-22, 公開日: 2017-05-03, 最終更新日: 2024-11-13)

主引用文献

Smith, G.F.,Altman, M.D.,Andresen, B.,Baker, J.,Brubaker, J.D.,Chen, H.,Chen, Y.,Childers, M.,Donofrio, A.,Ferguson, H.,Fischer, C.,Fischmann, T.O.,Gibeau, C.,Hicks, A.,Jin, S.,Kattar, S.,Kleinschek, M.A.,Leccese, E.,Lesburg, C.,Li, C.,Lim, J.,Liu, D.,Maclean, J.K.F.,Mansoor, F.,Moy, L.Y.,Mulrooney, E.F.,Necheva, A.S.,Presland, J.,Rakhilina, L.,Yang, R.,Torres, L.,Zhang-Hoover, J.,Northrup, A.
Identification of quinazoline based inhibitors of IRAK4 for the treatment of inflammation.
Bioorg. Med. Chem. Lett., 27:2721-2726, 2017

PubMed Abstract: Interleukin-1 receptor associated kinase 4 (IRAK4) has been implicated in IL-1R and TLR based signaling. Therefore selective inhibition of the kinase activity of this protein represents an attractive target for the treatment of inflammatory diseases. Medicinal chemistry optimization of high throughput screening (HTS) hits with the help of structure based drug design led to the identification of orally-bioavailable quinazoline based IRAK4 inhibitors with excellent pharmacokinetic profile and kinase selectivity. These highly selective IRAK4 compounds show activity in vivo via oral dosing in a TLR7 driven model of inflammation.

PubMed: 28501511
DOI: 10.1016/j.bmcl.2017.04.050

実験手法

X-RAY DIFFRACTION (2.34 Å)