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Title: Drug Mimicry: Promiscuous Receptors PXR and AhR, and Microbial Metabolite Interactions in the Intestine.

Authors: Dvořák, Zdeněk; Sokol, Harry; Mani, Sridhar

Published In Trends Pharmacol Sci, (2020 12)

Abstract: Significant attrition limits drug discovery. The available chemical entities present with drug-like features contribute to this limitation. Using specific examples of promiscuous receptor-ligand interactions, a case is made for expanding the chemical space for drug-like molecules. These ligand-receptor interactions are poor candidates for the drug discovery process. However, provided herein are specific examples of ligand-receptor or transcription-factor interactions, namely, the pregnane X receptor (PXR) and the aryl hydrocarbon receptor (AhR), and itsinteractions with microbial metabolites. Discrete examples of microbial metabolite mimicry are shown to yield more potent and non-toxic therapeutic leads for pathophysiological conditions regulated by PXR and AhR. These examples underscore the opinion that microbial metabolite mimicry of promiscuous ligand-receptor interactions is warranted, and will likely expand the existing chemical space of drugs.

PubMed ID: 33097284 Exiting the NIEHS site

MeSH Terms: Drug Discovery; Humans; Intestines; Pharmaceutical Preparations*; Pregnane X Receptor*; Receptors, Aryl Hydrocarbon*; Receptors, Steroid*

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