Author/Authors :
Robert Epple، نويسنده , , Mihai Azimioara، نويسنده , , Ross Russo، نويسنده , , Yongping Xie، نويسنده , , Xing Wang، نويسنده , , Christopher Cow، نويسنده , , John Wityak، نويسنده , , Don Karanewsky، نويسنده , , Badry Bursulaya، نويسنده , , Andreas Kreusch، نويسنده , , Tove Tuntland، نويسنده , , Andrea Gerken، نويسنده , , Maya Iskandar، نويسنده , , Enrique Saez، نويسنده , , H. Martin Seidel، نويسنده , , Shin-Shay Tian، نويسنده ,
Abstract :
A series of PPARδ-selective agonists was investigated and optimized for a favorable in vivo pharmacokinetic profile. Isoxazole LCI765 (17d) was found to be a potent and selective PPARδ agonist with good in vivo PK properties in mouse (Cmax = 5.1 μM, t1/2 = 3.1 h). LCI765 regulated expression of genes involved in energy homeostasis in relevant tissues when dosed orally in C57BL6 mice. A co-crystal structure of compound LCI765 and the LBD of PPARδ is discussed.
Keywords :
Metabolic xyndrome , isoxazoles , nuclear hormone receptor , PPAR? , Energy homeostasis , PPAR agonist
