2ieg
From Proteopedia
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| , resolution 1.90Å | |||||||
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| Ligands: | , | ||||||
| Activity: | Phosphorylase, with EC number 2.4.1.1 | ||||||
| Related: | 2IEI
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of rabbit muscle glycogen phosphorylase in complex with 3,4-dihydro-2-quinolone
Overview
A series of substituted 3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors, which have potential as antidiabetic agents, is described. Initial members of the series showed good enzyme inhibitory potency but poor physical properties. Optimisation of the 1-substituent led to 2,3-dihydroxypropyl compounds which showed good in vitro potency and improved physical properties, together with good DMPK profiles and acute in vivo efficacy in a rat model. X-ray crystallographic data are presented, showing an unexpected variety of binding orientations at the dimer interface site.
About this Structure
2IEG is a Single protein structure of sequence from Oryctolagus cuniculus. Full crystallographic information is available from OCA.
Reference
Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors., Birch AM, Kenny PW, Oikonomakos NG, Otterbein L, Schofield P, Whittamore PR, Whalley DP, Bioorg Med Chem Lett. 2007 Jan 15;17(2):394-9. Epub 2006 Oct 19. PMID:17095214
Page seeded by OCA on Mon Mar 31 03:43:12 2008
