1m7q
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Crystal structure of p38 MAP kinase in complex with a dihydroquinazolinone inhibitor
OverviewOverview
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).
About this StructureAbout this Structure
1M7Q is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
ReferenceReference
Design and synthesis of potent, orally bioavailable dihydroquinazolinone inhibitors of p38 MAP kinase., Stelmach JE, Liu L, Patel SB, Pivnichny JV, Scapin G, Singh S, Hop CE, Wang Z, Strauss JR, Cameron PM, Nichols EA, O'Keefe SJ, O'Neill EA, Schmatz DM, Schwartz CD, Thompson CM, Zaller DM, Doherty JB, Bioorg Med Chem Lett. 2003 Jan 20;13(2):277-80. PMID:12482439
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- Homo sapiens
- Single protein
- Cameron, P.M.
- Doherty, J.B
- Hop, C.E.C.A.
- Keefe, S.J.O.
- Liu, L.
- Neill, E.A.O.
- Nichols, E.A.
- Patel, S.B.
- Pivnichny, J.V.
- Scapin, G.
- Schmatz, D.M.
- Schwartz, C.D.
- Singh, S.
- Stelmach, J.E.
- Thompson, C.M.
- Wang, Z.
- Zaller, D.M.
- DQO
- SO4
- Atp-binding domain
- Inhibitor
- Serine/threonine kinase