3TTI

Crystal Structure of JNK3 complexed with CC-930, an orally active anti-fibrotic JNK inhibitor

3TTI の概要

• エントリーDOI: 10.2210/pdb3tti/pdb
• 関連するPDBエントリー: 3TTJ
• 分子名称: Mitogen-activated protein kinase 10, trans-4-({9-[(3S)-tetrahydrofuran-3-yl]-8-[(2,4,6-trifluorophenyl)amino]-9H-purin-2-yl}amino)cyclohexanol, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: mitogen-activated protein kinase 10, jnk3, protein kinase inhibitors, kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P53779
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 53189.87

構造登録者

Plantevin-Krenitsky, V.,Nadolny, L.,Delgado, M.,Ayala, L.,Clareen, S.,Hilgraf, R.,Albers, R.,Hegde, S.,D'Sidocky, N.,Sapienza, J.,Wright, J.,McCarrick, M.,Bahmanyar, S.,Chamberlain, P.,Delker, S.L.,Muir, J.,Giegel, D.,Xu, L.,Celeridad, M.,Lachowitzer, J.,Bennett, B.,Moghaddam, M.,Khatsenko, O.,Katz, J.,Fan, R.,Bai, A.,Tang, Y.,Shirley, M.A.,Benish, B.,Bodine, T.,Blease, K.,Raymon, H.,Cathers, B.E.,Satoh, Y. (登録日: 2011-09-14, 公開日: 2012-02-01, 最終更新日: 2024-02-28)

主引用文献

Plantevin Krenitsky, V.,Nadolny, L.,Delgado, M.,Ayala, L.,Clareen, S.S.,Hilgraf, R.,Albers, R.,Hegde, S.,D'Sidocky, N.,Sapienza, J.,Wright, J.,McCarrick, M.,Bahmanyar, S.,Chamberlain, P.,Delker, S.L.,Muir, J.,Giegel, D.,Xu, L.,Celeridad, M.,Lachowitzer, J.,Bennett, B.,Moghaddam, M.,Khatsenko, O.,Katz, J.,Fan, R.,Bai, A.,Tang, Y.,Shirley, M.A.,Benish, B.,Bodine, T.,Blease, K.,Raymon, H.,Cathers, B.E.,Satoh, Y.
Discovery of CC-930, an orally active anti-fibrotic JNK inhibitor.
Bioorg.Med.Chem.Lett., 22:1433-1438, 2012

PubMed Abstract: In this Letter we describe the discovery of potent, selective, and orally active aminopurine JNK inhibitors. Improving the physico-chemical properties as well as increasing the potency and selectivity of a subseries with rat plasma exposure, led to the identification of four structurally diverse inhibitors. Differentiation based on PK profiles in multiple species as well as activity in a chronic efficacy model led to the identification of 1 (CC-930) as a development candidate, which is currently in Phase II clinical trial for IPF.

PubMed: 22244937
DOI: 10.1016/j.bmcl.2011.12.027

実験手法

X-RAY DIFFRACTION (2.2 Å)