2. Academic Validation
  3. Avicholic Acid: A Lead Compound from Birds on the Route to Potent TGR5 Modulators

Avicholic Acid: A Lead Compound from Birds on the Route to Potent TGR5 Modulators

  • ACS Med Chem Lett. 2012 Feb 6;3(4):273-7. doi: 10.1021/ml200256d.
Roberto Pellicciari 1,  Antimo Gioiello 1,  Paola Sabbatini 1,  Francesco Venturoni 1,  Roberto Nuti 1,  Carolina Colliva 2,  Giovanni Rizzo 3,  Luciano Adorini 3,  Mark Pruzanski 3,  Aldo Roda 2,  Antonio Macchiarulo 1
Affiliations

Affiliations

  • 1 Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia , Via del Liceo 1, 06123 Perugia, Italy.
  • 2 Dipartimento di Scienze Farmaceutiche, Alma Mater Studiorum, Università di Bologna , Via Belmeloro 6, 40126 Bologna, Italy.
  • 3 Intercept Pharmaceuticals , New York, New York 10013, United States.
PMID: 24900463 DOI: 10.1021/ml200256d
Abstract

Grounding on our former 3D QSAR studies, a knowledge-based screen of natural bile acids from diverse animal species has led to the identification of avicholic acid as a selective but weak TGR5 agonist. Chemical modifications of this compound resulted in the disclosure of 6α-ethyl-16-epi-avicholic acid that shows enhanced potency at TGR5 and FXR receptors. The synthesis, biological appraisals, and structure-activity relationships of this series of compounds are herein described. Moreover, a thorough physicochemical characterization of 6α-ethyl-16-epi-avicholic acid as compared to naturally occurring bile acids is reported and discussed.

Keywords

16-epi-avicholic acid; CMC; FXR; TGR5; avicholic acid; bile acid; structure−activity relationship.

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