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— Phase 3 NASH Study
— Phase 4 PBC Study
— Phase 2 Biliary Atresia Study

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At Intercept, our work is motivated by our desire to help patients and families who struggle with chronic liver diseases and need better treatment options.

FXR


Introduction

  • FXR is a nuclear receptor expressed in the liver, intestine, kidney, and adipose tissue
  • FXR regulates a wide variety of target genes critically involved in the control of
    • BA synthesis and transport
    • Lipid metabolism
    • Glucose homeostasis
  • Intercept is pioneering the use of FXR agonism as a potential catalyst in anticholestatic and antifibrotic mechanisms

FXR agonism now represents a potential new treatment modality for many metabolic and liver conditions.


FXR resources: For in-depth clinical information

  1. 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity (Pelliciari et al, Journal of Medicinal Chemistry, August 2002)
  2. Targeting bile-acid signalling for metabolic diseases (Thomas et al, Nature Reviews Drug Discovery, August 2008)
  3. Role of bile acids and bile acid receptors in metabolic regulation (Lefebvre et al, Physiological Reviews, January 2009)
  4. A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis (Walters et al, Clinical Gastroenterology and Hepatology, November 2009)
  5. Farnesoid X Receptor Activation Prevents the Development of Vascular Calcification in ApoE-/- Mice With Chronic Kidney Disease (Miyazaki-Anzai, Circulation Research, April 2010)
  6. Deciphering the nuclear bile acid receptor FXR paradigm (Modica et al, Nuclear Receptor Signaling, Nov 2010)
  7. FGF19 as a Postprandial, Insulin-Independent Activator of Hepatic Protein and Glycogen Synthesis (Kir et al, Science, March 2011)
  8. Targeting nuclear bile acid receptors for liver disease (Trauner et al, Digestive Diseases, June 2011)
  9. Farnesoid x receptor agonists: what they are and how they might be used in treating liver disease (Neuschwander-Tetri, Current Gastroenterology Reports, February 2012)
  10. Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease (Porez, Journal of Lipid Research, September 2012)
  11. Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: an overview of their mechanisms of action. (Poupon, Clinics and Research in Hepatology and Gastroenterology, September 2012)
  12. Anti-inflammatory and metabolic actions of FXR: insights into molecular mechanisms. (Hollman et al, Biochima et Biophysica Acta., November 2012).
  13. FXR Agonist INT-747 Upregulates DDAH Expression and Enhances Insulin Sensitivity in High-Salt Fed Dahl Rats (Ghebremariam et al, PLoS One, April 2013)
  14. The FXR agonist normalizes insulin sensitivity in visceral preadipocytes of a rabbit model of MetS (Maneschi et al, The Journal of Endocrinology, June 2013)
  15. FXR is a molecular target for the effects of vertical sleeve gastrectomy (Ryan, Nature, May 2014)

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