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

Summary for 4IZY

• Entry DOI: 10.2210/pdb4izy/pdb
• Related: 4HYS 4HYU
• Descriptor: 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)
• Functional Keywords: kinase inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm (By similarity): Q9UQF2
• Total number of polymer chains: 2
• Total formula weight: 44403.40

Authors

Kuglstatter, A.,Shao, A. (deposition date: 2013-01-30, release date: 2013-12-18, Last modification date: 2023-09-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)