4AA0

P38ALPHA MAP KINASE BOUND TO CMPD 2

Summary for 4AA0

• Entry DOI: 10.2210/pdb4aa0/pdb
• Related: 1A9U 1BL6 1BL7 1BMK 1DI9 1IAN 1KV1 1KV2 1M7Q 1OUK 1OUY 1OVE 1OZ1 1R39 1R3C 1W7H 1W82 1W83 1W84 1WBN 1WBO 1WBS 1WBT 1WBV 1WBW 1WFC 1YQJ 1ZYJ 1ZZ2 1ZZL 2BAJ 2BAK 2BAL 2BAQ 2I0H 2Y8O 2YIS 2YIW 2YIX 3ZS5 3ZSG 3ZSH 3ZSI 3ZYA 4AA4 4AA5 4AAC
• Descriptor: MITOGEN-ACTIVATED PROTEIN KINASE 14, N-[4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxidanylidene-quinazolin-3-yl]phenyl]-2-morpholin-4-yl-pyridine-4-carboxamide (3 entities in total)
• Functional Keywords: serine/threonine kinase, transferase
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 42580.51

Authors

Gerhardt, S.,Hargreaves, D. (deposition date: 2011-11-30, release date: 2012-05-16, Last modification date: 2024-05-08)

Primary citation

Brown, D.S.,Cumming, J.G.,Bethel, P.,Finlayson, J.,Gerhardt, S.,Nash, I.,Pauptit, R.,Pike, K.G.,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]Benzamide (Azd6703), a Clinical P38Alpha Map Kinase Inhibitor for the Treatment of Inflammatory Diseases
Bioorg.Med.Chem.Lett., 22:3879-, 2012

PubMed Abstract: A novel, potent and selective quinazolinone series of inhibitors of p38α 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]benzamide (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.

PubMed: 22608965
DOI: 10.1016/J.BMCL.2012.04.116

Experimental method

X-RAY DIFFRACTION (1.8 Å)