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

Zdeněk Dvořák, Harry Sokol, Sridhar Mani

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

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 its interactions 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.

Original languageEnglish (US)
Pages (from-to)900-908
Number of pages9
JournalTrends in Pharmacological Sciences
Volume41
Issue number12
DOIs
StatePublished - Dec 2020

Keywords

  • biomimicry
  • chemical space
  • disease
  • drugs
  • metabolites
  • receptors

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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