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Elsevier, Bioorganic and Medicinal Chemistry, 23(19), p. 7168-7180, 2011

DOI: 10.1016/j.bmc.2011.09.056

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

Journal article published in 2011 by Daniela Schuster ORCID, Patrick Markt, Ulrike Grienke, Judit Mihaly-Bison, Markus Binder, Stefan M. Noha, Judith M. Rollinger, Hermann Stuppner, Valery N. Bochkov, Gerhard Wolber ORCID
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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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).