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

Drug Discovery Humans Intestines Pharmaceutical Preparations Pregnane X Receptor Receptors, Aryl Hydrocarbon Receptors, Steroid
biomimicry chemical space disease drugs metabolites receptors

Journal

Trends in pharmacological sciences
ISSN: 1873-3735
Titre abrégé: Trends Pharmacol Sci
Pays: England
ID NLM: 7906158

Informations de publication

Date de publication:
12 2020
Historique:
received: 06 07 2020
revised: 24 09 2020
accepted: 30 09 2020
pubmed: 25 10 2020
medline: 26 8 2021
entrez: 24 10 2020
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.tips.2020.09.013 PMID: 33097284 PMC: PMC7669654
pubmed: 33097284
pii: S0165-6147(20)30220-0
doi: 10.1016/j.tips.2020.09.013
pmc: PMC7669654
mid: NIHMS1635777
pii:
doi:

Substances chimiques

Pharmaceutical Preparations 0
Pregnane X Receptor 0
Receptors, Aryl Hydrocarbon 0
Receptors, Steroid 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

900-908

Subventions

Organisme : NCI NIH HHS
ID : R01 CA222469
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES030197
Pays : United States

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

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Auteurs

Zdeněk Dvořák (Z)

Departments of Cell Biology and Genetics, Palacký University, Olomouc 78371, Czech Republic. Electronic address: zdenek.dvorak@upol.cz.

Harry Sokol (H)

Sorbonne Université, Inserm, Centre de Recherche Saint-Antoine, CRSA, AP-HP, Hôpital Saint Antoine, Service de Gastroenterologie, F-75012 Paris, France; INRA, UMR 1319 Micalis and AgroParisTech, 78352 Jouy-en-Josas, France; Paris Centre for Microbiome Medicine FHU, Paris, France.

Sridhar Mani (S)

Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: sridhar.mani@einsteinmed.org.

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Classifications MeSH

questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Découverte de médicament › Drug Mimicry: Promiscuous Receptors PXR and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Drug Mimicry: Promiscuous Receptors PXR and...
questionsmedicales.fr › Système digestif › Tube digestif › Intestins › Drug Mimicry: Promiscuous Receptors PXR and...
questionsmedicales.fr › Préparations pharmaceutiques › Drug Mimicry: Promiscuous Receptors PXR and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Récepteurs aux stéroïdes › Récepteur du prégnane X › Drug Mimicry: Promiscuous Receptors PXR and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Récepteurs à hydrocarbure aromatique › Drug Mimicry: Promiscuous Receptors PXR and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Récepteurs aux stéroïdes › Drug Mimicry: Promiscuous Receptors PXR and...