Design of a partial PPARdelta agonist.
Structure based ligand design was used in order to design a partial agonist for the PPARdelta receptor. The maximum activation in the transactivation assay was reduced from 87% to 39%. The crystal structure of the ligand binding domain of the PPARdelta receptor in complex with compound 2 was determined in order to understand the structural changes which gave rise to the decrease in maximum activation.
Pettersson
Ingrid
I
Novo Nordisk A/S, Novo Nordisk Park, 2760 Måløv, Denmark. inpe@novonordisk.com
Ebdrup
Søren
S
Havranek
Miroslav
M
Pihera
Pavel
P
Korínek
Marek
M
Mogensen
John P
JP
Jeppesen
Claus B
CB
Johansson
Eva
E
Sauerberg
Per
P
D002087:Butyrates / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D008958:Models, Molecular; D015394:Molecular Structure; D047494:PPAR delta / Q000819:agonists*; D010671:Phenylurea Compounds / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*
D002087:Butyrates; C110636:GW 2433; C425931:GW 501516; D047494:PPAR delta; D010671:Phenylurea Compounds; D013844:Thiazoles