Evidence map›Paper›PMID 26633590›Full record

ArticleJournal of chemical information and modeling2016

Computational Prediction and Biochemical Analyses of New Inverse Agonists for the CB1 Receptor.

Caitlin E Scott, Kwang H Ahn, Steven T Graf, William A Goddard, Debra A Kendall, Ravinder Abrol

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of chemical information and modeling, 2016. 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
0.2field-weighted citation impact, top 42% 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, 5 citations in OpenAlex.

  1. 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

6 authors at 2 institutions in 1 country.

Caitlin E ScottMaterials and Process Simulation Center, Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
Kwang H AhnDepartment of Pharmaceutical Sciences, University of Connecticut , Storrs, Connecticut 06269, United States.
Steven T GrafDepartment of Pharmaceutical Sciences, University of Connecticut , Storrs, Connecticut 06269, United States.
William A GoddardMaterials and Process Simulation Center, Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
Debra A KendallDepartment of Pharmaceutical Sciences, University of Connecticut , Storrs, Connecticut 06269, United States.
Ravinder AbrolMaterials and Process Simulation Center, Division of Chemistry and Chemical Engineering, California Institute of Technology , Pasadena, California 91125, United States.
California Institute of Technology · USUniversity of Connecticut · US

Funding

Brain Endothelial Receptor for E. coliR01AI040567 · NIAID · CHILDREN'S HOSPITAL OF LOS ANGELES · PI DAVIS, MARK E, GODDARD, WILLIAM ANDREW · 2001 to 2015
$5.5M
Maneuvering of Macrophage Function By Escherichia coli K1R01NS073115 · NINDS · CHILDREN'S HOSPITAL OF LOS ANGELES · PI NEMANI, PRASADARAO V · 2010 to 2014
$1.6M
Determinants of the Cannabinoid Receptor Life CycleR01DA020763 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI KENDALL, DEBRA A · 2007 to 2011
$1.5M
Novel CB1 Inverse Agonists for Investigation of Constitutive Signaling ActivitiesR21DA038804 · NIDA · UNIVERSITY OF CONNECTICUT STORRS · PI KENDALL, DEBRA A · 2015 to 2016
$434k
NIAID NIH HHS R01 AI040567NIAID NIH HHS R01AI040567NIDA NIH HHS DA020763NIDA NIH HHS DA038804NIDA NIH HHS R01 DA020763NIDA NIH HHS R21 DA038804NINDS NIH HHS R01 NS073115NINDS NIH HHS R01NS073115
6 · The paper itself

Abstract

Human cannabinoid type 1 (CB1) G-protein coupled receptor is a potential therapeutic target for obesity. The previously predicted and experimentally validated ensemble of ligand-free conformations of CB1 [Scott, C. E. et al. Protein Sci. 2013 , 22 , 101 - 113 ; Ahn, K. H. et al. Proteins 2013 , 81 , 1304 - 1317] are used here to predict the binding sites for known CB1-selective inverse agonists including rimonabant and its seven known derivatives. This binding pocket, which differs significantly from previously published models, is used to identify 16 novel compounds expected to be CB1 inverse agonists by exploiting potential new interactions. We show experimentally that two of these compounds exhibit inverse agonist properties including inhibition of basal and agonist-induced G-protein coupling activity, as well as an enhanced level of CB1 cell surface localization. This demonstrates the utility of using the predicted binding sites for an ensemble of CB1 receptor structures for designing new CB1 inverse agonists.

Indexed as

Computational BiologyDrug Inverse AgonismBinding SitesDrug DiscoveryGene Expression RegulationHEK293 CellsHumansLigandsModels, MolecularPiperidinesProtein ConformationPyrazolesReceptor, Cannabinoid, CB1RimonabantStructure-Activity RelationshipLigandsPiperidinesPyrazolesReceptor, Cannabinoid, CB1Rimonabant

Identifiers

PMID26633590
PMCPMC4863456
OpenAlexW2233758214

What OpenQuestion holds

Textmetadata
Read underepoch 390

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 OpenQuestion graph.