Farnesoid X receptor: from medicinal chemistry to clinical applications

Future Medicinal Chemistry
Stefano FiorucciAngela Zampella

Abstract

The farnesoid X receptor (FXR) is a bile sensor that acts in coordination with other nuclear receptors to regulate essential steps in bile acid uptake, metabolism and excretion. In addition, FXR is an ancillary receptor involved in lipid and glucose homeostasis. Steroidal and non-steroidal FXR ligands are currently available. Both groups have shown limitations in the preclinical studies regarding absorption, metabolism, specificity of target and intrinsic toxicity. FXR ligands endowed with agonistic activity are under development for the treatment of cholestatic liver diseases, including primary biliary cirrhosis and metabolic disorders linked to insulin resistance. Despite the fact that results from preclinical models are encouraging, targeting FXR holds potential for side effects (i.e., impaired cholesterol disposal and cholestasis). Thus, results from FXR gene-ablated mice and mice administered an FXR antagonist support a role for FXR antagonists or modulators (i.e., FXR agonists that selectively activate specific subsets of FXR target genes in a tissue) or co-regulator-specific manner.

References

Jun 9, 1999·Molecular Cell·H WangB M Forman
Dec 24, 2002·The Journal of Biological Chemistry·Isabelle DussaultBarry M Forman
Sep 3, 2004·Journal of Lipid Research·Audrey SirventBart Staels
Oct 7, 2004·Molecular Genetics and Metabolism·Keith A HouckThomas P Burris
Dec 17, 2004·Molecular Pharmacology·Thomas P BurrisKeith R Stayrook
Feb 3, 2005·Gastroenterology·Christophe CorpechotRaoul Poupon
Aug 19, 2005·Journal of Medicinal Chemistry·Roberto PellicciariStefano Fiorucci
Feb 1, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Geoffrey C Farrell, Claire Z Larter
Apr 22, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Albert MennoneJames L Boyer
Jul 4, 2006·Trends in Endocrinology and Metabolism : TEM·Mark ChristianMalcolm G Parker
Jul 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Catherine StedmanMichael Downes
Dec 1, 2006·The New England Journal of Medicine·Renata BelfortKenneth Cusi
Jun 15, 2007·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Shi-Ying CaiJames L Boyer
Jun 26, 2007·Trends in Molecular Medicine·Stefano FiorucciLuca Santucci
Apr 9, 2008·Proceedings of the National Academy of Sciences of the United States of America·Stephen M SoissonJoseph W Becker
Jul 8, 2008·Journal of Pharmacological Sciences·Takuo SuzukiToru Kawanishi
Jul 16, 2008·Bioorganic & Medicinal Chemistry Letters·Adwoa Akwabi-AmeyawG Bruce Wisely
Nov 26, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Andrea MencarelliStefano Fiorucci
Apr 7, 2009·Journal of Lipid Research·John Y L Chiang
Nov 26, 2009·Progress in Lipid Research·Stefano FiorucciAndrea Mencarelli
Nov 28, 2009·Current Medicinal Chemistry·Stefano FiorucciSabrina Cipriani
Jan 12, 2010·Biochimica Et Biophysica Acta·Barbara RengaStefano Fiorucci
Aug 2, 2011·The Journal of Steroid Biochemistry and Molecular Biology·Johan W JonkerMichael Downes

❮ Previous
Next ❯

Citations

Oct 30, 2012·Journal of Chemical Information and Modeling·Weihua LiYun Tang
May 14, 2014·Nature Reviews. Endocrinology·Folkert KuipersAlbert K Groen
Feb 20, 2013·Current Pathobiology Reports·Xichun WangWendong Huang
Jan 3, 2015·Expert Opinion on Drug Metabolism & Toxicology·Ioannis KoutsounasConstantinos Giaginis
Feb 16, 2016·Journal of Medicinal Chemistry·Yanping Xu
Jul 2, 2015·Future Medicinal Chemistry·Valentina SepeAngela Zampella
Feb 25, 2015·Journal of Gastroenterology·Eleonora DistruttiStefano Fiorucci
Dec 15, 2012·Journal of Hepatology·Valerio NobiliPietro Vajro
Jan 15, 2015·Bioorganic & Medicinal Chemistry·Daniel MerkManfred Schubert-Zsilavecz
Apr 2, 2014·Bioorganic & Medicinal Chemistry·Daniel MerkManfred Schubert-Zsilavecz
Jun 14, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michele BiagioliStefano Fiorucci
Aug 2, 2017·Future Oncology·Constantinos GiaginisStamatios Theocharis
Sep 3, 2017·Journal of Computer-aided Molecular Design·Edithe SelwaBogdan I Iorga
Dec 15, 2017·Journal of Biomolecular Structure & Dynamics·Thales KronenbergerVinicius G Maltarollo
Jul 7, 2016·Scientific Reports·Claudia FinamoreAngela Zampella
Jul 31, 2014·Pharmacological Reviews·Tiangang Li, John Y L Chiang
Sep 21, 2018·Current Diabetes Reports·Karolina E Zaborska, Bethany P Cummings
Apr 16, 2021·ChemMedChem·Simone SchierleDaniel Merk

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation

Clinical Trials Mentioned

NCT00550862
NCT00501592

Related Concepts

Related Feeds

Atherosclerosis Disease Progression

Atherosclerosis is the buildup of plaque on artery walls, causing stenosis which can eventually lead to clinically apparent cardiovascular disease. Find the latest research on atherosclerosis disease progression here.