2P3G

Crystal structure of a pyrrolopyridine inhibitor bound to MAPKAP Kinase-2

Summary for 2P3G

• Entry DOI: 10.2210/pdb2p3g/pdb
• Related: 1KWP 1NXK 1NY3 2ONL
• Descriptor: MAP kinase-activated protein kinase 2, 2-[2-(2-FLUOROPHENYL)PYRIDIN-4-YL]-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE (2 entities in total)
• Functional Keywords: kinase domain, atp-binding, serine/threonine kinase, map kinases, mk-2, mk2, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P49137
• Total number of polymer chains: 1
• Total formula weight: 38205.07

Authors

Kurumbail, R.G.,Caspers, N. (deposition date: 2007-03-08, release date: 2007-06-12, Last modification date: 2024-04-03)

Primary citation

Anderson, D.R.,Meyers, M.J.,Vernier, W.F.,Mahoney, M.W.,Kurumbail, R.G.,Caspers, N.,Poda, G.I.,Schindler, J.F.,Reitz, D.B.,Mourey, R.J.
Pyrrolopyridine Inhibitors of Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK-2).
J.Med.Chem., 50:2647-2654, 2007

PubMed Abstract: A new class of potent kinase inhibitors selective for mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP-K2 or MK-2) for the treatment of rheumatoid arthritis has been prepared and evaluated. These inhibitors have IC50 values as low as 10 nM against the target and have good selectivity profiles against a number of kinases including CDK2, ERK, JNK, and p38. These MK-2 inhibitors have been shown to suppress TNFalpha production in U397 cells and to be efficacious in an acute inflammation model. The structure-activity relationships of this series, the selectivity for MK-2 and their activity in both in vitro and in vivo models are discussed. The observed selectivity is discussed with the aid of an MK-2/inhibitor crystal structure.

PubMed: 17480064
DOI: 10.1021/jm0611004

Experimental method

X-RAY DIFFRACTION (3.8 Å)