2gmx
Selective Aminopyridine-Based C-Jun N-terminal Kinase inhibitors with cellular activity
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OverviewOverview
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.
DiseaseDisease
Known diseases associated with this structure: Diabetes mellitus, noninsulin-dependent OMIM:[604641]
About this StructureAbout this Structure
2GMX is a Protein complex structure of sequences from Homo sapiens with SO4 and 877 as ligands. Active as Mitogen-activated protein kinase, with EC number 2.7.11.24 Full crystallographic information is available from OCA.
ReferenceReference
Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity., Szczepankiewicz BG, Kosogof C, Nelson LT, Liu G, Liu B, Zhao H, Serby MD, Xin Z, Liu M, Gum RJ, Haasch DL, Wang S, Clampit JE, Johnson EF, Lubben TH, Stashko MA, Olejniczak ET, Sun C, Dorwin SA, Haskins K, Abad-Zapatero C, Fry EH, Hutchins CW, Sham HL, Rondinone CM, Trevillyan JM, J Med Chem. 2006 Jun 15;49(12):3563-80. PMID:16759099
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