5cep | pdb_00005cep

DLK in complex with inhibitor N-(1-isopropyl-5-(piperidin-4-yl)-1H-pyrazol-3-yl)-4-(trifluoromethyl)pyridin-2-amine

spinqualitylabelsall models 5cep, resolution 1.99Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5cep is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 50E Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function M3K12_HUMAN May be an activator of the JNK/SAPK pathway. Phosphorylates beta-casein, histone 1 and myelin basic protein in vitro. Publication Abstract from PubMed Recent data suggest that inhibition of dual leucine zipper kinase (DLK, MAP3K12) has therapeutic potential for treatment of a number of indications ranging from acute neuronal injury to chronic neurodegenerative disease. Thus, high demand exists for selective small molecule DLK inhibitors with favorable drug-like properties and good CNS penetration. Herein we describe a shape-based scaffold hopping approach to convert pyrimidine 1 to a pyrazole core with improved physicochemical properties. We also present the first crystal structures of DLK. By utilizing a combination of property and structure-based design, we identified inhibitor 11, a potent, selective, and brain-penetrant inhibitor of DLK with activity in an in vivo nerve injury model. Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12).,Patel S, Harris SF, Gibbons P, Deshmukh G, Gustafson A, Kellar T, Lin H, Liu X, Liu Y, Liu Y, Ma C, Scearce-Levie K, Ghosh AS, Shin YG, Solanoy H, Wang J, Wang B, Yin J, Siu M, Lewcock JW J Med Chem. 2015 Oct 2. PMID:26431428 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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