5W86

CRYSTAL STRUCTURE OF JAK3 KINASE DOMAIN WITH A 4,6-DIAMINONICOTINAMIDE INHIBITOR (COMPOUND NUMBER 7)

5W86 の概要

• エントリーDOI: 10.2210/pdb5w86/pdb
• 関連するPDBエントリー: 5w84 5w85
• 分子名称: Tyrosine-protein kinase JAK3, 4-(benzylamino)-6-({4-[(1-methylpiperidin-4-yl)carbamoyl]phenyl}amino)pyridine-3-carboxamide (3 entities in total)
• 機能のキーワード: serine/threonine protein kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Endomembrane system ; Peripheral membrane protein : P52333
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 133267.94

構造登録者

Sack, J.S. (登録日: 2017-06-21, 公開日: 2017-10-11, 最終更新日: 2024-11-20)

主引用文献

Bhide, R.S.,Keon, A.,Weigelt, C.,Sack, J.S.,Schmidt, R.J.,Lin, S.,Xiao, H.Y.,Spergel, S.H.,Kempson, J.,Pitts, W.J.,Carman, J.,Poss, M.A.
Discovery and structure-based design of 4,6-diaminonicotinamides as potent and selective IRAK4 inhibitors.
Bioorg. Med. Chem. Lett., 27:4908-4913, 2017

PubMed Abstract: The identification of small molecule inhibitors of IRAK4 for the treatment of autoimmune diseases has been an area of intense research. We discovered novel 4,6-diaminonicotinamides which potently inhibit IRAK4. Optimization efforts were aided by X-ray crystal structures of inhibitors bound to IRAK4. Structure activity relationship (SAR) studies led to the identification of compound 29 which exhibited sub-micromolar potency in a LTA stimulated cellular assay.

PubMed: 28947151
DOI: 10.1016/j.bmcl.2017.09.029

実験手法

X-RAY DIFFRACTION (2.61 Å)