2GMX
Selective Aminopyridine-Based C-Jun N-terminal Kinase inhibitors with cellular activity
Summary for 2GMX
| Entry DOI | 10.2210/pdb2gmx/pdb |
| Related | 2g01 |
| Descriptor | Mitogen-activated protein kinase 8, C-jun-amino-terminal kinase-interacting protein 1, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | jnk1, c-jun n-terminal kinase, protein kinase jnk1 inhibitors, aminopyridine-based c-jun n-terminal kinase inhibitors, transcription |
| Biological source | Homo sapiens (human) More |
| Cellular location | Cytoplasm (By similarity): Q9UQF2 |
| Total number of polymer chains | 4 |
| Total formula weight | 89785.14 |
| Authors | Abad-Zapatero, C. (deposition date: 2006-04-07, release date: 2006-06-06, Last modification date: 2023-08-30) |
| Primary citation | Szczepankiewicz, B.G.,Kosogof, C.,Nelson, L.T.,Liu, G.,Liu, B.,Zhao, H.,Serby, M.D.,Xin, Z.,Liu, M.,Gum, R.J.,Haasch, D.L.,Wang, S.,Clampit, J.E.,Johnson, E.F.,Lubben, T.H.,Stashko, M.A.,Olejniczak, E.T.,Sun, C.,Dorwin, S.A.,Haskins, K.,Abad-Zapatero, C.,Fry, E.H.,Hutchins, C.W.,Sham, H.L.,Rondinone, C.M.,Trevillyan, J.M. Aminopyridine-Based c-Jun N-Terminal Kinase Inhibitors with Cellular Activity and Minimal Cross-Kinase Activity. J.Med.Chem., 49:3563-3580, 2006 Cited by PubMed Abstract: The c-Jun N-terminal kinases (JNK-1, -2, and -3) are members of the mitogen activated protein (MAP) kinase family of enzymes. They are activated in response to certain cytokines, as well as by cellular stresses including chemotoxins, peroxides, and irradiation. They have been implicated in the pathology of a variety of different diseases with an inflammatory component including asthma, stroke, Alzheimer's disease, and type 2 diabetes mellitus. In this work, high-throughput screening identified a JNK inhibitor with an excellent kinase selectivity profile. Using X-ray crystallography and biochemical screening to guide our lead optimization, we prepared compounds with inhibitory potencies in the low-double-digit nanomolar range, activity in whole cells, and pharmacokinetics suitable for in vivo use. The new compounds were over 1,000-fold selective for JNK-1 and -2 over other MAP kinases including ERK2, p38alpha, and p38delta and showed little inhibitory activity against a panel of 74 kinases. PubMed: 16759099DOI: 10.1021/jm060199b PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.5 Å) |
Structure validation
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