3CTQ

Structure of MAP kinase p38 in complex with a 1-o-tolyl-1,2,3-triazole-4-carboxamide

Summary for 3CTQ

• Entry DOI: 10.2210/pdb3ctq/pdb
• Descriptor: Mitogen-activated protein kinase 14, N-benzyl-1-[5-({5-tert-butyl-2-methoxy-3-[(methylsulfonyl)amino]phenyl}carbamoyl)-2-methylphenyl]-1H-1,2,3-triazole-4-carboxamide (3 entities in total)
• Functional Keywords: two lobe kinase fold, n-terminal beta-sheet, c-terminal alpha-helix, alternative splicing, atp-binding, cytoplasm, kinase, nucleotide-binding, nucleus, phosphoprotein, polymorphism, serine/threonine-protein kinase, transferase
• Biological source: Homo sapiens (man)
• Cellular location: Cytoplasm: Q16539
• Total number of polymer chains: 1
• Total formula weight: 40391.28

Authors

Qian, K. (deposition date: 2008-04-14, release date: 2008-05-27, Last modification date: 2024-02-21)

Primary citation

Cogan, D.A.,Aungst, R.,Breinlinger, E.C.,Fadra, T.,Goldberg, D.R.,Hao, M.H.,Kroe, R.,Moss, N.,Pargellis, C.,Qian, K.C.,Swinamer, A.D.
Structure-based design and subsequent optimization of 2-tolyl-(1,2,3-triazol-1-yl-4-carboxamide) inhibitors of p38 MAP kinase.
Bioorg.Med.Chem.Lett., 18:3251-3255, 2008

PubMed Abstract: A computer-aided drug design strategy leads to the identification of a new class of p38 inhibitors based on the 2-tolyl-(1,2,3-triazol-1-yl-4-carboxamide) scaffold. The tolyl triazole amides provided a potent platform amenable to optimization. Further exploration leads to compounds with greater than 100-fold improvement in binding affinity to p38. Derivatives prepared to alter the physicochemical properties produced inhibitors with IC(50)'s in human whole blood as low as 83 nM.

PubMed: 18462940
DOI: 10.1016/j.bmcl.2008.04.043

Experimental method

X-RAY DIFFRACTION (1.95 Å)