4L7F

Co-crystal Structure of JNK1 and AX13587

4L7F の概要

• エントリーDOI: 10.2210/pdb4l7f/pdb
• 分子名称: Mitogen-activated protein kinase 8, N-[1-(4-fluorophenyl)cyclopropyl]-4-[(trans-4-hydroxycyclohexyl)amino]imidazo[1,2-a]quinoxaline-8-carboxamide (3 entities in total)
• 機能のキーワード: protein kinase fold, protein kinase, jun-c, phosphorylation, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P45983
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42836.62

構造登録者

Walter, R.L.,Ranieri, G.M.,Riggs, A.M.,Weissig, H.,Li, B.,Shreder, K.R. (登録日: 2013-06-13, 公開日: 2013-08-21, 最終更新日: 2024-02-28)

主引用文献

Li, B.,Cociorva, O.M.,Nomanbhoy, T.,Weissig, H.,Li, Q.,Nakamura, K.,Liyanage, M.,Zhang, M.C.,Shih, A.Y.,Aban, A.,Hu, Y.,Cajica, J.,Pham, L.,Kozarich, J.W.,Shreder, K.R.
Hit-to-lead optimization and kinase selectivity of imidazo[1,2-a]quinoxalin-4-amine derived JNK1 inhibitors.
Bioorg.Med.Chem.Lett., 23:5217-5222, 2013

PubMed Abstract: As the result of a rhJNK1 HTS, the imidazo[1,2-a]quinoxaline 1 was identified as a 1.6 μM rhJNK1 inhibitor. Optimization of this compound lead to AX13587 (rhJNK1 IC50=160 nM) which was co-crystallized with JNK1 to identify key molecular interactions. Kinase profiling against 125+ kinases revealed AX13587 was an inhibitor of JNK, MAST3, and MAST4 whereas its methylene homolog AX14373 (native JNK1 IC50=47 nM) was a highly specific JNK inhibitor.

PubMed: 23916259
DOI: 10.1016/j.bmcl.2013.06.087

実験手法

X-RAY DIFFRACTION (1.95 Å)