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 language | English (US) |
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Pages (from-to) | 900-908 |
Number of pages | 9 |
Journal | Trends in Pharmacological Sciences |
Volume | 41 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2020 |
Keywords
- biomimicry
- chemical space
- disease
- drugs
- metabolites
- receptors
ASJC Scopus subject areas
- Toxicology
- Pharmacology