4ZTN

Irak4-inhibitor co-structure

4ZTN の概要

• エントリーDOI: 10.2210/pdb4ztn/pdb
• 関連するPDBエントリー: 4ZTL 4ZTM
• 分子名称: Interleukin-1 receptor-associated kinase 4, 5-(1,3-benzothiazol-2-yl)-2-(morpholin-4-yl)-6-[(3R)-piperidin-3-ylamino]pyrimidin-4(3H)-one (3 entities in total)
• 機能のキーワード: kinase, 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: 137474.82

構造登録者

Fischmann, T.O. (登録日: 2015-05-14, 公開日: 2015-09-02, 最終更新日: 2024-11-13)

主引用文献

Seganish, W.M.,Fischmann, T.O.,Sherborne, B.,Matasi, J.,Lavey, B.,McElroy, W.T.,Tulshian, D.,Tata, J.,Sondey, C.,Garlisi, C.G.,Devito, K.,Fossetta, J.,Lundell, D.,Niu, X.
Discovery and Structure Enabled Synthesis of 2,6-Diaminopyrimidin-4-one IRAK4 Inhibitors.
Acs Med.Chem.Lett., 6:942-947, 2015

PubMed Abstract: We report the identification and synthesis of a series of aminopyrimidin-4-one IRAK4 inhibitors. Through high throughput screening, an aminopyrimidine hit was identified and modified via structure enabled design to generate a new, potent, and kinase selective pyrimidin-4-one chemotype. This chemotype is exemplified by compound 16, which has potent IRAK4 inhibition activity (IC50 = 27 nM) and excellent kinase selectivity (>100-fold against 99% of 111 tested kinases), and compound 31, which displays potent IRAK4 activity (IC50 = 93 nM) and good rat bioavailability (F = 42%).

PubMed: 26288698
DOI: 10.1021/acsmedchemlett.5b00279

実験手法

X-RAY DIFFRACTION (2.23 Å)