3PTG

Design and Synthesis of a Novel, Orally Efficacious Tri-substituted Thiophene Based JNK Inhibitor

3PTG の概要

• エントリーDOI: 10.2210/pdb3ptg/pdb
• 分子名称: Mitogen-activated protein kinase 10, C-Jun-amino-terminal kinase-interacting protein 1, N-[4-methyl-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl]-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide, ... (4 entities in total)
• 機能のキーワード: jnk inhibitor, thiophene, neurodegeneration, 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: P53779; Cytoplasm (By similarity): Q9UQF2
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 43583.48

構造登録者

Bowers, S.,Truong, A.P.,Neitz, J.,Neitzel, M.,Probst, G.D.,Hom, R.K.,Konradi, A.W.,Sham, H.L.,Toth, G.,Pan, H.,Yao, N.,Artis, D.R.,Brigham, E.F.,Quinn, K.P.,Sauer, J.,Powell, K.,Ruslim, L.,Bard, F.,Yednock, T.A.,Griswold-Prenner, I. (登録日: 2010-12-02, 公開日: 2011-03-02, 最終更新日: 2024-02-21)

主引用文献

Bowers, S.,Truong, A.P.,Neitz, R.J.,Neitzel, M.,Probst, G.D.,Hom, R.K.,Peterson, B.,Galemmo, R.A.,Konradi, A.W.,Sham, H.L.,Toth, G.,Pan, H.,Yao, N.,Artis, D.R.,Brigham, E.F.,Quinn, K.P.,Sauer, J.M.,Powell, K.,Ruslim, L.,Ren, Z.,Bard, F.,Yednock, T.A.,Griswold-Prenner, I.
Design and synthesis of a novel, orally active, brain penetrant, tri-substituted thiophene based JNK inhibitor.
Bioorg.Med.Chem.Lett., 21:1838-1843, 2011

PubMed Abstract: The SAR of a series of tri-substituted thiophene JNK3 inhibitors is described. By optimizing both the N-aryl acetamide region of the inhibitor and the 4-position of the thiophene we obtained single digit nanomolar compounds, such as 47, which demonstrated an in vivo effect on JNK activity when dosed orally in our kainic acid mouse model as measured by phospho-c-jun reduction.

PubMed: 21316234
DOI: 10.1016/j.bmcl.2011.01.046

実験手法

X-RAY DIFFRACTION (2.43 Å)