5LMB

HUMAN SPLEEN TYROSINE KINASE KINASE DOMAIN IN COMPLEX WITH AZANAPHTHYRIDINE INHIBITOR

5LMB の概要

• エントリーDOI: 10.2210/pdb5lmb/pdb
• 関連するPDBエントリー: 5LMA
• 分子名称: Tyrosine-protein kinase SYK, 7-[6-(dimethylamino)pyridin-3-yl]-~{N}-[[(3~{S})-piperidin-3-yl]methyl]pyrido[3,4-b]pyrazin-5-amine, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: inhibitor, complex, kinase, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65695.56

構造登録者

Somers, D.O.,Neu, M. (登録日: 2016-07-29, 公開日: 2016-09-14, 最終更新日: 2024-11-06)

主引用文献

Garton, N.S.,Barker, M.D.,Davis, R.P.,Douault, C.,Hooper-Greenhill, E.,Jones, E.,Lewis, H.D.,Liddle, J.,Lugo, D.,McCleary, S.,Preston, A.G.,Ramirez-Molina, C.,Neu, M.,Shipley, T.J.,Somers, D.O.,Watson, R.J.,Wilson, D.M.
Optimisation of a novel series of potent and orally bioavailable azanaphthyridine SYK inhibitors.
Bioorg.Med.Chem.Lett., 26:4606-4612, 2016

PubMed Abstract: The optimisation of the azanaphthyridine series of Spleen Tyrosine Kinase inhibitors is described. The medicinal chemistry strategy was focused on optimising the human whole blood activity whilst achieving a sufficient margin over hERG activity. A good pharmacokinetic profile was achieved by modification of the pKa. Morpholine compound 32 is a potent SYK inhibitor showing moderate selectivity, good oral bioavailability and good efficacy in the rat Arthus model but demonstrated a genotoxic potential in the Ames assay.

PubMed: 27578246
DOI: 10.1016/j.bmcl.2016.08.070

実験手法

X-RAY DIFFRACTION (1.95 Å)