1M7Q

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

1M7Q の概要

• エントリーDOI: 10.2210/pdb1m7q/pdb
• 分子名称: 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)
• 機能のキーワード: serine/threonine kinase, atp-binding domain, inhibitor, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : Q16539
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 42584.35

構造登録者

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. (登録日: 2002-07-22, 公開日: 2002-12-11, 最終更新日: 2024-02-14)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.4 Å)