4Y73

Crystal structure of IRAK4 kinase domain with inhibitor

4Y73 の概要

• エントリーDOI: 10.2210/pdb4y73/pdb
• 分子名称: Interleukin-1 receptor-associated kinase 4, 5-{[(1R,2S)-2-aminocyclohexyl]amino}-N-[1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (3 entities in total)
• 機能のキーワード: kinase, inhibitor, transferase
• 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: 137742.62

構造登録者

Lesburg, C.A. (登録日: 2015-02-13, 公開日: 2015-05-20, 最終更新日: 2024-10-16)

主引用文献

Lim, J.,Altman, M.D.,Baker, J.,Brubaker, J.D.,Chen, H.,Chen, Y.,Fischmann, T.,Gibeau, C.,Kleinschek, M.A.,Leccese, E.,Lesburg, C.,Maclean, J.K.,Moy, L.Y.,Mulrooney, E.F.,Presland, J.,Rakhilina, L.,Smith, G.F.,Steinhuebel, D.,Yang, R.
Discovery of 5-Amino-N-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide Inhibitors of IRAK4.
Acs Med.Chem.Lett., 6:683-688, 2015

PubMed Abstract: Interleukin-1 receptor associated kinase 4 (IRAK4) is an essential signal transducer downstream of the IL-1R and TLR superfamily, and selective inhibition of the kinase activity of the protein represents an attractive target for the treatment of inflammatory diseases. A series of 5-amino-N-(1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamides was developed via sequential modifications to the 5-position of the pyrazolopyrimidine ring and the 3-position of the pyrazole ring. Replacement of substituents responsible for poor permeability and improvement of physical properties guided by cLogD led to the identification of IRAK4 inhibitors with excellent potency, kinase selectivity, and pharmacokinetic properties suitable for oral dosing.

PubMed: 26101574
DOI: 10.1021/acsmedchemlett.5b00107

実験手法

X-RAY DIFFRACTION (2.14 Å)