Peroxisome proliferator-activated receptors (PPARs) are ligand-ac- tivated transcription factors that govern lipid and glucose ho- meostasis, and play a central role in cardiovascular disease, obe- sity, and diabetes. Thus, there is significant interest in developing new and specific agonists for these receptors. Herein we present screening results for a series of chiral phenoxyacetic acid ana- logues, some of which are potent PPARa agonists as well as PPARg agonists. The stereochemistry of these compounds plays an important role in determining their activity ; the S isomers were observed to be more active than the corresponding R isom- ers. Interestingly, for one of these analogues, the stereoselectivity toward PPARa was reversed, and for this reason docking experi- ments were performed to rationalize this peculiar behavior.

Bile acid signaling to the nucleus: finding new connections in the transcriptional regulation of metabolic pathways / E. De Fabiani, N. Mitro, C. Godio, F. Gilardi, D. Caruso, M. Crestani. - In: BIOCHIMIE. - ISSN 0300-9084. - 86:11(2004 Nov), pp. 771-778.

Bile acid signaling to the nucleus: finding new connections in the transcriptional regulation of metabolic pathways

E. De Fabiani
Primo
;
N. Mitro
Secondo
;
C. Godio;F. Gilardi;D. Caruso
Penultimo
;
M. Crestani
Ultimo
2004

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-ac- tivated transcription factors that govern lipid and glucose ho- meostasis, and play a central role in cardiovascular disease, obe- sity, and diabetes. Thus, there is significant interest in developing new and specific agonists for these receptors. Herein we present screening results for a series of chiral phenoxyacetic acid ana- logues, some of which are potent PPARa agonists as well as PPARg agonists. The stereochemistry of these compounds plays an important role in determining their activity ; the S isomers were observed to be more active than the corresponding R isom- ers. Interestingly, for one of these analogues, the stereoselectivity toward PPARa was reversed, and for this reason docking experi- ments were performed to rationalize this peculiar behavior.
Bile acids; Gene transcription; Glucose metabolism; Lipid metabolism; Liver; Nuclear receptors
Settore BIO/10 - Biochimica
nov-2004
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/28579
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