4IZY

Crystal structure of JNK1 in complex with JIP1 peptide and 4-{4-[4-(4-Methanesulfonyl-piperidin-1-yl)-indol-1-yl]-pyrimidin-2-ylamino}-cyclohexan

4IZY の概要

• エントリーDOI: 10.2210/pdb4izy/pdb
• 関連するPDBエントリー: 4HYS 4HYU
• 分子名称: Mitogen-activated protein kinase 8, C-Jun-amino-terminal kinase-interacting protein 1, trans-4-[(4-{4-[4-(methylsulfonyl)piperidin-1-yl]-1H-indol-1-yl}pyrimidin-2-yl)amino]cyclohexanol, ... (4 entities in total)
• 機能のキーワード: kinase inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm (By similarity): Q9UQF2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 44403.40

構造登録者

Kuglstatter, A.,Shao, A. (登録日: 2013-01-30, 公開日: 2013-12-18, 最終更新日: 2023-09-20)

主引用文献

Gong, L.,Han, X.,Silva, T.,Tan, Y.C.,Goyal, B.,Tivitmahaisoon, P.,Trejo, A.,Palmer, W.,Hogg, H.,Jahagir, A.,Alam, M.,Wagner, P.,Stein, K.,Filonova, L.,Loe, B.,Makra, F.,Rotstein, D.,Rapatova, L.,Dunn, J.,Zuo, F.,Dal Porto, J.,Wong, B.,Jin, S.,Chang, A.,Tran, P.,Hsieh, G.,Niu, L.,Shao, A.,Reuter, D.,Hermann, J.,Kuglstatter, A.,Goldstein, D.
Development of indole/indazole-aminopyrimidines as inhibitors of c-Jun N-terminal kinase (JNK): optimization for JNK potency and physicochemical properties.
Bioorg.Med.Chem.Lett., 23:3565-3569, 2013

PubMed Abstract: A novel series of indole/indazole-aminopyrimidines was designed and synthesized with an aim to achieve optimal potency and selectivity for the c-Jun kinase family or JNKs. Structure guided design was used to optimize the series resulting in a significant potency improvement. The best compound (17) has IC50 of 3 nM for JNK1 and 20 nM for JNK2, with greater than 40-fold selectivity against other kinases with good physicochemical and pharmacokinetic properties.

PubMed: 23664880
DOI: 10.1016/j.bmcl.2013.04.029

実験手法

X-RAY DIFFRACTION (2.3 Å)