Ki: 6 nM for PPARγ
Peroxisome proliferator-activated receptor (PPARγ) is known to be expressed ubiquitously and involved in lipid and glucose metabolism. Studies have demonstrated that PPARγ is expressed in endothelial cells and plays a potential role in endothelial proliferation and survival. L-165041 is reported as a selective and potent PPARγ ligand.
In vitro: L-165041, which is a selective and potent PPARδligand, displayed in this specified transactivation system, apart from its highly efficacious PPARδ agonist activity, partial and full agonism at, respectively, PPARγ2 and PPARαsubtypes [1].
In vivo: L-165041 could drastically reduce lipid accumulation in the mouse liver, decreasing total hepatic triglyceride and cholesterol content compared to the vehicle group. Gene analysis demonstrated that L-165041 lowered hepatic expression of PPARγ, apolipoprotein B, IL-1β, and interleukin-6. In contrast, L-165041 increased hepatic expressions of PPARδ, lipoprotein lipase, and ATP-binding cassette transporter G1 (ABCG1) [2].
Clinical trial: Up to now, L-165041 is still in the preclinical development stage.
Reference:
[1] Wurch T, Junquero D, Delhon A, Pauwels J. Pharmacological analysis of wild-type alpha, gamma and delta subtypes of the human peroxisome proliferator-activated receptor. Naunyn Schmiedebergs Arch Pharmacol. 2002 Feb;365(2):133-40.
[2] Lim HJ, Park JH, Lee S, Choi HE, Lee KS, Park HY. PPARdelta ligand L-165041 ameliorates Western diet-induced hepatic lipid accumulation and inflammation in LDLR-/- mice. Eur J Pharmacol. 2009 Nov 10;622(1-3):45-51.