3RTP

Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration

3RTP の概要

• エントリーDOI: 10.2210/pdb3rtp/pdb
• 分子名称: Mitogen-activated protein kinase 10, N-[4-cyano-3-(1H-1,2,4-triazol-5-yl)thiophen-2-yl]-2-(2-oxo-3,4-dihydroquinolin-1(2H)-yl)acetamide (3 entities in total)
• 機能のキーワード: jnk inhibitors, pharmacokinetic properties, neurodegeneration, 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: 42248.85

構造登録者

Bowers, S.,Truong, A.P.,Neitz, R.J.,Hom, R.K.,Sealy, J.M.,Probst, G.D.,Quincy, Q.,Peterson, B.,Chan, W.,Galemmo Jr., R.A.,Konradi, A.W.,Sham, H.L.,Pan, H.,Lin, M.,Yao, N.,Artis, D.R.,Zhang, H.,Chen, L.,Dryer, M.,Samant, B.,Zmolek, W.,Wong, K.,Lorentzen, C.,Goldbach, E.,Tonn, G.,Quinn, K.P.,Sauer, J.,Wright, S.,Powell, K.,Ruslim, L.,Ren, Z.,Bard, F.,Yednock, T.A.,Griswold-Prenne, I. (登録日: 2011-05-03, 公開日: 2013-05-08, 最終更新日: 2024-02-28)

主引用文献

Bowers, S.,Truong, A.P.,Jeffrey Neitz, R.,Hom, R.K.,Sealy, J.M.,Probst, G.D.,Quincy, D.,Peterson, B.,Chan, W.,Galemmo, R.A.,Konradi, A.W.,Sham, H.L.,Toth, G.,Pan, H.,Lin, M.,Yao, N.,Artis, D.R.,Zhang, H.,Chen, L.,Dryer, M.,Samant, B.,Zmolek, W.,Wong, K.,Lorentzen, C.,Goldbach, E.,Tonn, G.,Quinn, K.P.,Sauer, J.M.,Wright, S.,Powell, K.,Ruslim, L.,Ren, Z.,Bard, F.,Yednock, T.A.,Griswold-Prenner, I.
Design and synthesis of brain penetrant selective JNK inhibitors with improved pharmacokinetic properties for the prevention of neurodegeneration.
Bioorg.Med.Chem.Lett., 21:5521-5527, 2011

PubMed Abstract: The SAR of a series of brain penetrant, trisubstituted thiophene based JNK inhibitors with improved pharmacokinetic properties is described. These compounds were designed based on information derived from metabolite identification studies which led to compounds such as 42 with lower clearance, greater brain exposure and longer half life compared to earlier analogs.

PubMed: 21813278
DOI: 10.1016/j.bmcl.2011.06.100

実験手法

X-RAY DIFFRACTION (2.4 Å)