Target Validation Information
Target ID T36557
Target Name Peroxisomeproliferator activated receptor delta
Target Type
Clinical Trial
Drug Potency against Target L-165461 Drug Info IC50 = 4 nM [526582]
Netoglitazone Drug Info EC50 = 3000 nM [552339]
L-796449 Drug Info IC50 = 6 nM [526582]
Action against Disease Model Netoglitazone Netoglitazone is a thiazolidinedione, which acts as either a full or partial PPAR-gamma agonist, or antagonist, in a cell type specific manner, The pro-adipocytic and anti-osteoblastic activities of netoglitazone were evaluated in vitro, using both U-33/gamma2 cells as a model of marrow mesenchymal cell differentiation under the control of PPAR-gamma2 and primary bone marrowcultures, and in vivo in C57BL/6 mice. In vitro, netoglitazone induced adipocyte and inhibited osteoblast formation in a PPAR-gamma2-dependent manner; however, it was 100-fold less effective than rosiglitazone. In vivo, the administration of netoglitazone at an effective hyperglycemic dose (10 microg/g body weight/day) did not result in trabecular bone loss. Bone quality parameters such as bone mineral density and bone microarchitecture were not affected in netoglitazone-treated animals. The observed lack of an in vivo effect of netoglitazone on bone was entirely consistent with its low anti-osteoblastic activity in vitro [552545] Drug Info
The Effect of Target Knockout, Knockdown or Genetic Variations We investigated the consequences of inducible short-term PPARdelta knockout in the adult mouse heart. In addition to a substantial transcriptional downregulation of lipid metabolic proteins, short-term PPARdelta knockout in the adult mouse heart attenuated cardiac expression of both Cu/Zn superoxide dismutase and manganese superoxide dismutase, leading to increased oxidativedamage to the heart. Moreover, expression of key mitochondrial biogenesis determinants such as PPARgamma coactivator-1 were substantially decreased in the short-term PPARdelta deficient heart, concomitant with a decreased mitochondrial DNA copy n uMber. Rates of palmitate and glucose oxidation were markedly depressed in cardiomyocytes of PPARdelta knockout hearts. Consequently, PPARdelta deficiency in the adult heart led to depressed cardiac performance and cardiac hypertrophy.PPARdelta is an essential regulator of cardiac mitochondrial protection and biogenesis and PPARdelta activation can be a potential therapeutic target for cardiac disorders. [552545]
References
Ref 552545Netoglitazone is a PPAR-gamma ligand with selective effects on bone and fat. Bone. 2006 Jan;38(1):74-84. Epub 2005 Aug 30.
Ref 526582Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80.Phenylacetic acid derivatives as hPPAR agonists.
Ref 552339Treatment of non-insulin-dependent diabetes mellitus. Expert Opin Investig Drugs. 2003 Apr;12(4):623-33.
Ref 526582Bioorg Med Chem Lett. 2003 Apr 7;13(7):1277-80.Phenylacetic acid derivatives as hPPAR agonists.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.