2. Academic Validation
  3. Pharmacophore-based discovery of FXR agonists. Part I: Model development and experimental validation

Pharmacophore-based discovery of FXR agonists. Part I: Model development and experimental validation

  • Bioorg Med Chem. 2011 Dec 1;19(23):7168-80. doi: 10.1016/j.bmc.2011.09.056.
Daniela Schuster 1,  Patrick Markt,  Ulrike Grienke,  Judit Mihaly-Bison,  Markus Binder,  Stefan M Noha,  Judith M Rollinger,  Hermann Stuppner,  Valery N Bochkov,  Gerhard Wolber
Affiliations

Affiliation

  • 1 Computer-Aided Molecular Design Group, Institute of Pharmacy, Department of Pharmaceutical Chemistry, Center for Molecular Biosciences Innsbruck - CMBI, University of Innsbruck, Innrain 52c, A-6020 Innsbruck, Austria. Daniela.Schuster@uibk.ac.at
PMID: 22018919 DOI: 10.1016/j.bmc.2011.09.056
Abstract

The farnesoid X receptor (FXR) is involved in glucose and lipid metabolism regulation, which makes it an attractive target for the metabolic syndrome, dyslipidemia, atherosclerosis, and type 2 diabetes. In order to find novel FXR agonists, a structure-based pharmacophore model collection was developed and theoretically evaluated against virtual databases including the ChEMBL database. The most suitable models were used to screen the National Cancer Institute (NCI) database. Biological evaluation of virtual hits led to the discovery of a novel FXR Agonist with a piperazine scaffold (compound 19) that shows comparable activity as the endogenous FXR Agonist chenodeoxycholic acid (CDCA, compound 2).

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