1M7Q

Crystal structure of p38 MAP kinase in complex with a dihydroquinazolinone inhibitor

Summary for 1M7Q

• Entry DOI: 10.2210/pdb1m7q/pdb
• Descriptor: Mitogen-activated protein kinase 14, SULFATE ION, 1-(2,6-DICHLOROPHENYL)-5-(2,4-DIFLUOROPHENYL)-7-PIPERAZIN-1-YL-3,4-DIHYDROQUINAZOLIN-2(1H)-ONE, ... (4 entities in total)
• Functional Keywords: serine/threonine kinase, atp-binding domain, inhibitor, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q16539
• Total number of polymer chains: 1
• Total formula weight: 42584.35

Authors

Stelmach, J.E.,Liu, L.,Patel, S.B.,Pivnichny, J.V.,Scapin, G.,Singh, S.,Hop, C.E.C.A.,Wang, Z.,Cameron, P.M.,Nichols, E.A.,O'Keefe, S.J.,O'Neill, E.A.,Schmatz, D.M.,Schwartz, C.D.,Thompson, C.M.,Zaller, D.M.,Doherty, J.B. (deposition date: 2002-07-22, release date: 2002-12-11, Last modification date: 2024-02-14)

Primary citation

Stelmach, J.E.,Liu, L.,Patel, S.B.,Pivnichny, J.V.,Scapin, G.,Singh, S.,Hop, C.E.,Wang, Z.,Strauss, J.R.,Cameron, P.M.,Nichols, E.A.,O'Keefe, S.J.,O'Neill, E.A.,Schmatz, D.M.,Schwartz, C.D.,Thompson, C.M.,Zaller, D.M.,Doherty, J.B.
Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase.
Bioorg.Med.Chem.Lett., 13:277-280, 2003

PubMed Abstract: The development of potent, orally bioavailable (in rat) and selective dihydroquinazolinone inhibitors of p38alpha MAP kinase is described. These analogues are hybrids of a pyridinylimidazole p38alpha inhibitor reported by Merck Research Laboratories and VX-745. Optimization of the C-5 phenyl and the C-7 piperidinyl substituents led to the identification of 15i which gave excellent suppression of TNF-alpha production in LPS-stimulated whole blood (IC(50)=10nM) and good oral exposure in rats (F=68%, AUCn PO=0.58 microM h).

PubMed: 12482439
DOI: 10.1016/S0960-894X(02)00752-7

Experimental method

X-RAY DIFFRACTION (2.4 Å)