Biological Activity
bms 687453 is a pparα agonist.the peroxisome proliferator activated receptor (ppar) is a member of the intracellular nuclear hormone receptor superfamily of transcription factors, having pleiotropic effects on plasma lipoprotein levels, insulin sensitization, atherosclerosis, and inflammation.
in vitro
bms-687453 was identified as a potent and selective ppar alpha agonist, with approximately 410-fold selectivity versus human ppargamma in ppar-gal4 transactivation assays. in addition, similar potency and selectivity were also seen in the full length receptor co-transfection assays. [1].
in vivo
in previous study, bms-687453 had an excellent pharmacokinetic profile across all tested animal species. the oral absorption was rapid in mouse, rat, dog, and cynomulgus monkey. bms-687453 also exhibited low plasma clearance in the mouse, rat, and monkey and moderate plasma clearance in the dog. the half-life of bms-687453 ranged from 3 h in mouse to 12 h in cynomolgus monkeys. bms-687453 showed excellent absolute oral bioavailability ranging from 58% (dog) to 91% (rat) [1].
IC 50
10 nm for human pparα
References
[1] li j. discovery of an oxybenzylglycine based peroxisome proliferator activated receptor alpha selective agonist 2-((3-((2-(4-chlorophenyl)-5-methyloxazol-4-yl)methoxy)benzyl)(methoxycarbonyl) amino)acetic acid (bms-687453). j med chem. 2010 apr 8;53(7):2854-64.
