2IEG

Crystal structure of rabbit muscle glycogen phosphorylase in complex with 3,4-dihydro-2-quinolone

Summary for 2IEG

• Entry DOI: 10.2210/pdb2ieg/pdb
• Related: 2IEI
• Descriptor: Glycogen phosphorylase, muscle form, (5-HYDROXY-4,6-DIMETHYLPYRIDIN-3-YL)METHYL DIHYDROGEN PHOSPHATE, (2S)-N-[(3S)-1-(2-AMINO-2-OXOETHYL)-2-OXO-1,2,3,4-TETRAHYDROQUINOLIN-3-YL]-2-CHLORO-2H-THIENO[2,3-B]PYRROLE-5-CARBOXAMIDE, ... (4 entities in total)
• Functional Keywords: glycogen phosphorylase, glypho, diabetes, transferase
• Biological source: Oryctolagus cuniculus (rabbit)
• Total number of polymer chains: 2
• Total formula weight: 195854.43

Authors

Birch, A.M.,Kenny, P.W.,Oikonomakos, N.G.,Otterbein, L.,Schofield, P.,Whittamore, P.R.O.,Whalley, D.P.,Rowsell, S.,Pauptit, R.,Pannifer, A.,Breed, J.,Minshull, C. (deposition date: 2006-09-19, release date: 2006-12-26, Last modification date: 2024-12-25)

Primary citation

Birch, A.M.,Kenny, P.W.,Oikonomakos, N.G.,Otterbein, L.,Schofield, P.,Whittamore, P.R.,Whalley, D.P.
Development of potent, orally active 1-substituted-3,4-dihydro-2-quinolone glycogen phosphorylase inhibitors.
Bioorg.Med.Chem.Lett., 17:394-399, 2007

PubMed Abstract: 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.

PubMed: 17095214
DOI: 10.1016/j.bmcl.2006.10.037

Experimental method

X-RAY DIFFRACTION (1.9 Å)