Estimation of the receptor-state affinity constants of ligands in functional studies using wild type and constitutively active mutant receptors: Implications for estimation of agonist bias.

Frederick J Ehlert, Richard S L Stein

Open access · greenAbstract read

In one paragraph

Article in Journal of pharmacological and toxicological methods. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it

0cells of the map it votes in

1citing papers in PubMed

0.3field-weighted citation impact, top 31% of its field

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

1 citing paper in PubMed, 4 citations in OpenAlex.

A single unified model for fitting simple to complex receptor response data.Scientific reports · 2020
Article

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Frederick J EhlertDepartment of Pharmacology, School of Medicine, University of California, Irvine, Irvine, CA 92697-4625, United States; Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697-4625, United States. Electronic address: fjehlert@uci.edu.

Richard S L SteinDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697-4625, United States.

University of California, Irvine · US

Funding

University of California Health Participation in the National COVID Cohort Collaborative (N3C)UL1TR001414 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI COOPER, DAN M, VILAIN, ERIC J. · 2015 to 2023

$35.1M

NCATS NIH HHS UL1 TR001414

6 · The paper itself

Abstract

We describe a method for estimating the affinities of ligands for active and inactive states of a G protein-coupled receptor (GPCR). Our protocol involves measuring agonist-induced signaling responses of a wild type GPCR and a constitutively active mutant of it under control conditions and after partial receptor inactivation or reduced receptor expression. Our subsequent analysis is based on the assumption that the activating mutation increases receptor isomerization into the active state without affecting the affinities of ligands for receptor states. A means of confirming this assumption is provided. Global nonlinear regression analysis yields estimates of 1) the active (K

Indexed as

Drug AgonismModels, BiologicalBinding SitesComputer SimulationDose-Response Relationship, DrugHumansLigandsMolecular Docking SimulationMonte Carlo MethodMutationNonlinear DynamicsProtein BindingReceptors, G-Protein-CoupledRegression AnalysisSignal TransductionStructure-Activity RelationshipLigandsReceptors, G-Protein-CoupledActive stateAgonist biasConstitutive activityEfficacyInactive stateMonod-Wyman-Changeux modelObserved affinityReceptor activationReceptor state affinity constantsSystem bias

Identifiers

PMID27725245

DOI10.1016/j.vascn.2016.09.007

PMCPMC5769967

OpenAlexW2531246842

What Socratic holds

Textmetadata

LicenceTDM

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Registered trials

None linked

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 Socratic graph.