3TTI

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

Summary for 3TTI

• Entry DOI: 10.2210/pdb3tti/pdb
• Related: 3TTJ
• Descriptor: 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)
• Functional Keywords: mitogen-activated protein kinase 10, jnk3, protein kinase inhibitors, kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P53779
• Total number of polymer chains: 1
• Total formula weight: 53189.87

Authors

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. (deposition date: 2011-09-14, release date: 2012-02-01, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.2 Å)