Ligands PPAR

Figure 3 provides a very general overview of transcriptional activation in response to a PPAR ligand. Fig. 3a shows the schematic representation of a PPAR target gene in the absence of PPAR ligand. Co-repressor proteins bound to both unliganded PPAR and RXR... 

Peroxisome Proliferator-Activated Receptors. Figure 3 Transcription of PPAR target genes. A schematic representation of the transcription of PPAR-regulated genes in the absence (a) and presence (b) of PPAR ligand. Abbreviations PPAR-RE, peroxisome proliferator-activated receptor-response element RNA Pol II, RNA polymerase II TATA-BP, TATA-binding protein. 

Straus, D. S., and Glass, C. K. (2007). Anti-inflammatory actions of PPAR ligands New insights on cellular and molecular mechanisms. Trends Immunol. 28, 551-558. 

There are several reports of fish PPARs. A full-length PPARy was cloned from the Atlantic salmon (Salmo salarf. Multiple variants of PPARy are expressed in the salmon liver. PPAR ligands caused increased expression of PPARy and acyl-CoA... 

PPAR ligands with the ability to simultaneously activate all three receptor isotypes have the potential to address the adverse metabolic and cardiovascular liabilities associated with T2D, with concomitant reduction of the common side-effects associated with the PPARy agonists. 

Etgen, G.J. and Mantlo, N. (2003) PPAR ligands for metabolic disorders. Current Topics in Medicinal Chemistry, 3, 1649-1661. 

Troglitazone PPAR ligand FTC133, follicular cancer cell line X ... 

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. 

Markt, P., Schuster, D., Kirchmair, J., Laggner, C., and Langer, T. (2007) Pharmacophore modeling and parallel screening for PPAR ligands. Journal of Computer-Aided Molecular Design, 21, 575-590. 

Inc., Santa Fe, NM, 2007). From the resulting 10 virtual screening hits, 5 were active in PPAR ligand binding domain transactivation assays on either one or two of these subtypes (Figure 12.12). 

Discovery of novel PPAR ligands by a virtual screening approach based on pharmacophore modelling, 3D shape, and electrostatic similarity screening. Journal of Medicinal Chemistry, 51, 6303-6317. 

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