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Inside Cover: Design and Biological Evaluation of Novel, Balanced Dual PPARα/γ Agonists (ChemMedChem 6/2009)
Author(s) -
Grether Uwe,
Bénardeau Agnes,
Benz Jörg,
Binggeli Alfred,
Blum Denise,
Hilpert Hans,
Kuhn Bernd,
Märki Hans Peter,
Meyer Markus,
Mohr Peter,
Püntener Kurt,
Raab Susanne,
Ruf Armin,
Schlatter Daniel
Publication year - 2009
Publication title -
chemmedchem
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200990027
Subject(s) - agonist , chemistry , peroxisome proliferator activated receptor , cover (algebra) , selectivity , alkoxy group , stereochemistry , residue (chemistry) , ic50 , combinatorial chemistry , receptor , biochemistry , in vitro , organic chemistry , mechanical engineering , alkyl , engineering , catalysis
Abstract The inside cover picture shows the X‐ray‐determined binding of an α‐ethoxy‐phenyl‐propionic acid‐derived dual PPARα/γ agonist in complex with PPARα (yellow) and PPARγ (blue). The high α‐selectivity of this phenylthiazole (IC 50 γ/α = 37; EC 50 γ/α = 7) can be rationalized mainly by a single residue difference, Cys 275 (α) vs. Gly 284 (γ), leading to three additional interactions with the terminal p ‐Cl‐Ph group. In addition, its binding site is highlighted in a surface representation of the PPARα protein. For more details, see the Communication by U. Grether et al. on p. 951 ff.