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pp 1-29 | Cite as

Chemistry and Pharmacology of GPBAR1 and FXR Selective Agonists, Dual Agonists, and Antagonists

  • Simona De Marino
  • Carmen Festa
  • Valentina Sepe
  • Angela ZampellaEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series

Abstract

In the recent years, bile acid receptors FXR and GPBAR1 have attracted the interest of scientific community and companies, as they proved promising targets for the treatment of several diseases, ranging from liver cholestatic disorders to metabolic syndrome, inflammatory states, nonalcoholic steatohepatitis (NASH), and diabetes.

Consequently, the development of dual FXR/GPBAR1 agonists, as well as selective targeting of one of these receptors, is considered a hopeful possibility in the treatment of these disorders. Because endogenous bile acids and steroidal ligands, which cover the same chemical space of bile acids, often target both receptor families, speculation on nonsteroidal ligands represents a promising and innovative strategy to selectively target GPBAR1 or FXR.

In this review, we summarize the most recent acquisition on natural, semisynthetic, and synthetic steroidal and nonsteroidal ligands, able to interact with FXR and GPBAR1.

Keywords

Bile acid receptors Farnesoid X receptor (FXR) G-protein-coupled receptor (GPBAR1) Natural ligands Semisynthetic ligands Synthetic ligands 

Abbreviations

ANIT

Alpha-naphthylisothiocyanate

BSEP

Bile salt export pump

CDCA

Chenodeoxycholic acid

DIO

Diet-induced obesity

HFD

High-fat diet

NAFLD

Nonalcoholic fatty liver disease

NASH

Nonalcoholic steatohepatitis

PBC

Primary biliary cirrhosis

SHP

Small heterodimer partner

UDCA

Ursodeoxycholic acid

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Simona De Marino
    • 1
  • Carmen Festa
    • 1
  • Valentina Sepe
    • 1
  • Angela Zampella
    • 1
    Email author
  1. 1.Department of PharmacyUniversity of Naples “Federico II”NaplesItaly

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