1OZ1

P38 MITOGEN-ACTIVATED KINASE IN COMPLEX WITH 4-AZAINDOLE INHIBITOR

Summary for 1OZ1

• Entry DOI: 10.2210/pdb1oz1/pdb
• Descriptor: Mitogen-activated protein kinase 14, 3-(4-FLUOROPHENYL)-2-PYRIDIN-4-YL-1H-PYRROLO[3,2-B]PYRIDIN-1-OL (3 entities in total)
• Functional Keywords: ser/thr protein kinase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): Q16539
• Total number of polymer chains: 1
• Total formula weight: 43054.02

Authors

Lovejoy, B.,Villasenor, A.,Browner, M.,Dunten, P. (deposition date: 2003-04-07, release date: 2003-09-23, Last modification date: 2024-02-14)

Primary citation

Trejo, A.,Arzeno, H.,Browner, M.,Chanda, S.,Cheng, S.,Comer, D.D.,Dalrymple, S.A.,Dunten, P.,Lafargue, J.,Lovejoy, B.,Freire-Moar, J.,Lim, J.,Mcintosh, J.,Miller, J.,Papp, E.,Reuter, D.,Roberts, R.,Sanpablo, F.,Saunders, J.,Song, K.,Villasenor, A.,Warren, S.D.,Welch, M.,Weller, P.,Whiteley, P.E.,Zeng, L.,Goldstein, D.M.
Design and synthesis of 4-azaindoles as inhibitors of p38 MAP kinase.
J.Med.Chem., 46:4702-4713, 2003

PubMed Abstract: Inhibition of the biosynthesis of proinflammatory cytokines such as tumor necrosis factor and interleukin-1 via p38 has been an approach toward the development of a disease modifying agent for the treatment of chronic inflammation and autoimmune diseases. The development of a new core structure of p38 inhibitors, 3-(4-fluorophenyl)-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b] pyridine, is described. X-ray crystallographic data of the lead bound to the active site of p38 was used to guide the optimization of the series. Specific focus was placed on modulating the physical properties of the core while maintaining potent inhibition of p38. These efforts identified 42c as a potent inhibitor of p38, which also possessed the required physical properties worthy of advanced studies.

PubMed: 14561090
DOI: 10.1021/jm0301787

Experimental method

X-RAY DIFFRACTION (2.1 Å)