Selective peroxisome proliferator activated

Schupp, M., Clemenz, M., Gineste, R., Witt, H., Janke, J., Helleboid, S., Hennuer, N., Ruiz, P., Unger, T., Staels, B., and Kintscher, U. (2005). Molecular characterization of new selective peroxisome proliferator-activated receptor y modulators with angiotensin receptor blocking activity. Diabetes 54, 3442-3452. 

Halofenate is a selective peroxisome proliferator-activated receptor y modulator with antidiabetic activity. Diabetes, 55, 2523-2533. 

Rieusset, J., Touri, F., Michalik, L. et al. (2002) A new selective peroxisome proliferator-activated receptor y antagonist with antiobesity antidiabetic activity. Molecular Endocrinology, 16, 2628-2644. 

Mukherjee, R., Hoener, P.A., Jow, L. et al. (2000) A selective peroxisome proliferator-activated receptor y (PPARy) modulator blocks adipocyte differentiation but... 

Another group has evaluated self-organizing maps [63] and shape/ pharmacophore models [64]. They developed a new method termed SQUIRREL to compare molecules in terms of both shape and pharmacophore points. Thus from a commercial library of 199,272 compounds, 1926 were selected based on self-organizing maps trained on peroxisome proliferator-activated receptor a (PPARa) "activity islands." The compounds were further evaluated with SQUIRREL and 7 out of 21 molecules selected were found to be active in PPARa. Furthermore, a new virtual screening technique (PhAST) was developed based on representation of molecules as text strings that describe their pharmacophores [65]. 

HP-jS-CD were added. All compounds were resolved in 20 min (see Figure 5). The data indicated that the validated method offered equivalent and complementary information, in terms of selectivity, sensitivity, accuracy, linearity, and precision, to that of an established gradient LC method employed for similar purposes. Ragaglitazar is a dual peroxisome proliferator-activated receptor ot and y agonist intended to restore insulin sensitivity and correct diabetic dyslipidemia. A chiral CZE method combining two CDs, sulfobutylether-jS-CD and dimethyl-/i-CD, lent itself to the analysis of ragaglitazar, its distomer (the (+)... 

Berger J.P., Petro A.E., Macnaul K.L., Kelly L.J., Zhang B.B., Richards K., Elbrecht A., Johnson B.A., Zhou G., Doebber T.W., et al. Distinct properties and advantages of a novel peroxisome proliferator-activated protein [gamma] selective modulator. Mol. Endocrinol. 2003, 17, 662-676. 

Netoglitazone is an insulin sensitizer currently in Phase II clinical trials. It is able to modulate both PPAR-a and PPAR-y subtypes of peroxisome proliferator-activated receptor (Phase ll). Metaglidasen (MBX-102) is the (—)-enantiomer of the NSAID halofenate. This selective PPAR-y nuclear receptor agonist is being evaluated (Phase II) as an insulin sensitizer. It is structurally different from the currently marketed glitazones (Figure 8.84). ... 

Mechanism of Action Potent and highly selective agonist for peroxisome proliferator-activated receptor-gamma (PPAR(gamma)) which decreases insulin resistance in the periphery and in the liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. 

Martin, G., Poirier, H., Hennuyer, N., Crombie, D., Fruchart, J. C., Heyman, R. A., Besnard, P., and Auwerx, J. (2000). Induction Of The Fatty Acid Transport Protein 1 and Acyl-Coa Synthase Genes by Dimer-Selective Rexinoids Suggests That the Peroxisome Proliferator-Activated Receptor-Retinoid X Receptor Heterodimer is Their Molecular Target./ Bid. Chem. 275, 12612-12618. 

Xu, H.E. etal. Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors, Proc. Natl Acad. Sci. USA, 24, 13919, 2001. 

Sugden MC, Bulmer K, Augustine D, and Holness MJ (2001a) Selective modification of pyruvate dehydrogenase kinase isoform expression in rat pancreatic islets elicited by starvation and activation of peroxisome proliferator-activated receptor-alpha implications for glucose-stimulated insulin secretion. Diabetes 50, 2729-36. 

---