Allosteric modulators restore orthosteric agonist binding to mutated CB

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Article in The Journal of pharmacy and pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed, 2 citations in OpenAlex.

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4 · The record

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5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Rachel DopartDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA.

Debra A KendallDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, USA.ORCID https://orcid.org/0000-0002-4991-9953

University of Connecticut · US

Funding

CB1 Allosteric Modulators: Molecular, Cellular and In Vivo PharmacologyR01DA039942 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI KINSEY, STEVEN G., LICHTMAN, ARON H · 2016 to 2020

$2.6M

NIDA NIH HHS R01 DA039942NIH HHS DA039942

6 · The paper itself

Abstract

objectivesTo determine if diminished orthosteric agonist binding due to mutations in extracellular loops 1 or 2 of the cannabinoid receptor 1 (CB

methodsBinding assays were performed using a range of concentrations of orthosteric compound, in the presence or absence of a set concentration of the allosteric modulator PSNCBAM-1 to determine the EC KEY

findingsSingle mutations in extracellular loop 1 or 2 of CB

conclusionsBased on our findings, we provide evidence of a therapeutic application for allosteric modulators in situations where a mutation in the receptor may hinder its function. By utilizing allosteric modulators, restoration of orthosteric binding may be possible.

Indexed as

Binding SitesCannabinoid Receptor AgonistsCyclohexanolsHEK293 CellsHumansIndolesLigandsMutationPhenylurea CompoundsPiperidinesProtein BindingProtein ConformationPyridinesReceptor, Cannabinoid, CB1RimonabantStructure-Activity Relationship1-(4-chlorophenyl)-3-(3-(6-pyrrolidin-1-ylpyridin-2-yl)phenyl)urea3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol5-chloro-3-ethyl-1H-indole-2-carboxylic acid (2-(4-piperidin-1-yl-phenyl)ethyl)amideCannabinoid Receptor AgonistsCNR1 protein, humanCyclohexanolsIndolesLigandsPhenylurea CompoundsPiperidinesPyridinesReceptor, Cannabinoid, CB1Rimonabantcannabinoid receptor 1G protein-coupled receptorligand bindingpositive allosteric modulatorPSNCBAM-1

Identifiers

PMID31722122

DOI10.1111/jphp.13193

PMCPMC6906232

OpenAlexW2987106024

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.