3OCG

P38 Alpha kinase complexed with a 5-amino-pyrazole based inhibitor

3OCG の概要

• エントリーDOI: 10.2210/pdb3ocg/pdb
• 分子名称: Mitogen-activated protein kinase 14, 5-amino-N-[5-(isoxazol-3-ylcarbamoyl)-2-methylphenyl]-1-phenyl-1H-pyrazole-4-carboxamide (3 entities in total)
• 機能のキーワード: p38 map kinase, serine/threonine-protein kinase, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42507.41

構造登録者

Sack, J.S. (登録日: 2010-08-10, 公開日: 2010-11-17, 最終更新日: 2024-02-21)

主引用文献

Das, J.,Moquin, R.V.,Dyckman, A.J.,Li, T.,Pitt, S.,Zhang, R.,Shen, D.R.,McIntyre, K.W.,Gillooly, K.,Doweyko, A.M.,Newitt, J.A.,Sack, J.S.,Zhang, H.,Kiefer, S.E.,Kish, K.,McKinnon, M.,Barrish, J.C.,Dodd, J.H.,Schieven, G.L.,Leftheris, K.
5-Amino-pyrazoles as potent and selective p38α inhibitors
Bioorg.Med.Chem.Lett., 20:6886-6889, 2010

PubMed Abstract: The synthesis and structure-activity relationships (SAR) of p38α MAP kinase inhibitors based on a 5-amino-pyrazole scaffold are described. These studies led to the identification of compound 2j as a potent and selective inhibitor of p38α MAP kinase with excellent cellular potency toward the inhibition of TNFα production. Compound 2j was highly efficacious in vivo in inhibiting TNFα production in an acute murine model of TNFα production. X-ray co-crystallography of a 5-amino-pyrazole analog 2f bound to unphosphorylated p38α is also disclosed.

PubMed: 21035336
DOI: 10.1016/j.bmcl.2010.10.034

実験手法

X-RAY DIFFRACTION (2.21 Å)