3U8W

Crystal Structure of p38a Mitogen-Activated Protein Kinase in Complex with a Triazolopyridazinone inhibitor

3U8W の概要

• エントリーDOI: 10.2210/pdb3u8w/pdb
• 関連するPDBエントリー: 1YQJ 3DS6 3DT1 3GFE 3ITZ 3LHJ
• 分子名称: Mitogen-activated protein kinase 14, 3-[3-(2-chloro-6-fluorophenyl)-5-ethyl-6-oxo-5,6-dihydro[1,2,4]triazolo[4,3-b]pyridazin-7-yl]-N-cyclopropyl-4-methylbenzamide (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: Cytoplasm: Q16539
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42464.85

構造登録者

Mohr, C.,Jordan, S. (登録日: 2011-10-17, 公開日: 2012-08-29, 最終更新日: 2024-02-28)

主引用文献

Herberich, B.,Jackson, C.,Wurz, R.P.,Pettus, L.H.,Sherman, L.,Liu, Q.,Henkle, B.,Saris, C.J.,Wong, L.M.,Chmait, S.,Lee, M.R.,Mohr, C.,Hsieh, F.,Tasker, A.S.
Identification of triazolopyridazinones as potent p38alpha inhibitors.
Bioorg.Med.Chem.Lett., 22:1226-1229, 2012

PubMed Abstract: Structure-activity relationship (SAR) investigations of a novel class of triazolopyridazinone p38α mitogen activated protein kinase (MAPK) inhibitors are disclosed. From these studies, increased in vitro potency was observed for 2,6-disubstituted phenyl moieties and N-ethyl triazolopyridazinone cores due to key contacts with Leu108, Ala157 and Val38. Further investigation led to the identification of three compounds, 3g, 3j and 3m that are highly potent inhibitors of LPS-induced MAPKAP kinase 2 (MK2) phosphorylation in 50% human whole blood (hWB), and possess desirable in vivo pharmacokinetic and kinase selectivity profiles.

PubMed: 22196117
DOI: 10.1016/j.bmcl.2011.11.067

実験手法

X-RAY DIFFRACTION (2.15 Å)