| Structural highlights
4aac is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | ,
| | Related: | 2baj, 1wfc, 3zsi, 1w7h, 1wbo, 1kv2, 1bmk, 1yqj, 1bl7, 1zyj, 1a9u, 1wbt, 2i0h, 3zs5, 2yiw, 2baq, 1wbv, 1zz2, 1di9, 1w83, 1bl6, 3zsh, 1m7q, 1ian, 1oz1, 1wbn, 3zya, 2bak, 3zsg, 1wbs, 2bal, 1ouk, 1ouy, 2y8o, 2yis, 1r39, 1wbw, 1kv1, 1w82, 2yix, 1r3c, 1ove, 1w84, 1zzl |
| Activity: | Mitogen-activated protein kinase, with EC number 2.7.11.24 |
| Resources: | FirstGlance, OCA, RCSB, PDBsum |
Publication Abstract from PubMed
A novel, potent and selective quinazolinone series of inhibitors of p38alpha MAP kinase has been identified. Modifications designed to address the issues of poor aqueous solubility and high plasma protein binding as well as embedded aniline functionalities resulted in the identification of a clinical candidate N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]ben zamide (AZD6703). Optimisation was guided by understanding of the binding modes from X-ray crystallographic studies which showed a switch from DFG 'out' to DFG 'in' as the inhibitor size was reduced to improve overall properties.
The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]ben zamide (AZD6703), a clinical p38alpha MAP kinase inhibitor for the treatment of inflammatory diseases.,Brown DS, Cumming JG, Bethel P, Finlayson J, Gerhardt S, Nash I, Pauptit RA, Pike KG, Reid A, Snelson W, Swallow S, Thompson C Bioorg Med Chem Lett. 2012 Jun 15;22(12):3879-83. Epub 2012 May 2. PMID:22608965[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Brown DS, Cumming JG, Bethel P, Finlayson J, Gerhardt S, Nash I, Pauptit RA, Pike KG, Reid A, Snelson W, Swallow S, Thompson C. The discovery of N-cyclopropyl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]ben zamide (AZD6703), a clinical p38alpha MAP kinase inhibitor for the treatment of inflammatory diseases. Bioorg Med Chem Lett. 2012 Jun 15;22(12):3879-83. Epub 2012 May 2. PMID:22608965 doi:10.1016/j.bmcl.2012.04.116
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