PPAR inhibitor

These compounds belong to the class of a-aryloxy-p-phenyl propionic acids, the first dual PPAR inhibitors with an aryloxy group on the a-carbon in relation to the carboxylic group, represented by the lead compotmd, (S)-5. 

The thiazolidinediones have also been reported to act as inhibitors of the respiratory chain at high concentrations, and this appears to account for their ability to activate AMGPK in cultured cells. However, the primary target of the thiazolidinediones appears to be the peroxisome proliferator-activated receptor-y ( PPAR-y), a member of the nuclear receptor superfamily expressed in adipocytes. One of the major effects of stimulation of PPAR-y in adipocytes is the release ofthe... 

HMG-CoA-Reductase-Inhibitors Peroxisome Proliferator-Activated Recqrtors (PPARs) ACE Inhibitors Antiplatelet Drugs... 

Peroxisome Proliferator-Activated Receptor (PPARs) HMG-CoA Reductase Inhibitors... 

Fibrates work by reducing apolipoproteins B, C-III (an inhibitor of LPL), and E, and increasing apolipoproteins A-I and A-II through activation of peroxisome proliferator-activated receptors-alpha (PPAR-a), a nuclear receptor involved in cellular function. The changes in these apolipoproteins result in a reduction in triglyceride-rich lipoproteins (VLDL and IDL) and an increase in HDL. 

Several fluorine-containing drugs are currently in development for the treatment of diabetes. These are peroxisome proliferator-activated nuclear receptor (PPAR) agonists, aldose reductase, and dipeptidylpeptidase IV (DPP-IV) inhibitors. 

PPAR-y inhibitors consisting of lH-indole-2-carboxylate derivatives, (III), and (3-aryl-a-hydroxy propionic acid derivatives, (IV), prepared by Stolle (3) and Gurram (4), respectively, were effective in the treatment of diseases caused by increased fat accumulation or lipid storage, such as osteoporosis, obesity, and acne. 

Although the three remaining subsites of the PPAR LED exhibited less variation than the distal pockets, the CRID/CPCA calculations revealed some scope for selective interactions, in particular with the OH and C3 probes within the linker and head regions. This analysis agreed well with site-directed mutagenesis experiments, as well as the selectivity of known inhibitors. 

T 22573 Troglitazone Antitumor agent PPAR-y agonist induces apoptosis via a p53 pathway. Microtube Inhibitors ... 

Since then, approximately 70 studies have been reported in the literature, and far more have been conducted internally within pharmaceutical companies, documenting the effectiveness of cTn as a biomarker to identify, assess, and monitor preclinical cardiac toxicity (O Brien 2008). This has been demonstrated for several classes of drugs, including adrenergic agents, agonists of peroxisome proliferator-activated receptors (PPAR especially for alpha-PPARs), anthracyclines and other anticancer drugs, and phosphodiesterase inhibitors. 

More than 70% of differentiated thyroid cancer concentrates radioiodine after TSH stimulation (Robbins et al., 1991 Jarzab et al., 2003). Some differentiated thyroid cancer (approximately 10-20%), as well as anaplastic thyroid cancer, however, do not concentrate radioiodide, even after TSH stimulation (Robbins et al., 1991). Since almost all differentiated thyroid cancer expresses TSHR (Brabant et al, 1991), the absence of NIS induction in response to TSH is most likely due to defects in postreceptor signaling pathways. Recent studies have demonstrated the potential for NIS induction in poorly differentiated thyroid cancer by redifferentiation agents, such as nuclear receptor ligands, RA and peroxisome proliferator-activated receptor- (PPAR ) ligands, and inhibitors of epigenetic modifications. 

---