Evidence map›Paper›PMID 22285942›Full record

ArticleBioorganic & medicinal chemistry letters2012

3D-QSAR and 3D-QSSR models of negative allosteric modulators facilitate the design of a novel selective antagonist of human α4β2 neuronal nicotinic acetylcholine receptors.

Brandon J Henderson, Crina M Orac, Iwona Maciagiewicz, Stephen C Bergmeier, Dennis B McKay

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.4field-weighted citation impact, top 38% 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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. Allosteric transition: a comparison of two models.BMC pharmacology & toxicology · 2013
    Article
  4. 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

5 authors at 2 institutions in 1 country.

Brandon J HendersonDivision of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA. mckay.2@osu.edu
Crina M Orac
Iwona Maciagiewicz
Stephen C Bergmeier
Dennis B McKay
Ohio University · USThe Ohio State University · US

Funding

Novel lead molecule optimization targeting nicotinic receptor subtypesR21DA029433 · NIDA · OHIO STATE UNIVERSITY · PI LI, CHENGLONG, MCKAY, DENNIS BRIAN · 2009 to 2010
$508k
NIDA NIH HHS DA029433NIDA NIH HHS R21 DA029433
6 · The paper itself

Abstract

Subtype selective molecules for α4β2 neuronal nicotinic acetylcholine receptors (nAChRs) have been sought as novel therapeutics for nicotine cessation. α4β2 nAChRs have been shown to be involved in mediating the addictive properties of nicotine while other subtypes (i.e., α3β4 and α7) are believed to mediate the undesired effects of potential CNS drugs. To obtain selective molecules, it is important to understand the physiochemical features of ligands that affect selectivity and potency on nAChR subtypes. Here we present novel QSAR/QSSR models for negative allosteric modulators of human α4β2 nAChRs and human α3β4 nAChRs. These models support previous homology model and site-directed mutagenesis studies that suggest a novel mechanism of antagonism. Additionally, information from the models presented in this work was used to synthesize novel molecules; which subsequently led to the discovery of a new selective antagonist of human α4β2 nAChRs.

Indexed as

Drug DesignModels, MolecularAllosteric SiteBinding, CompetitiveBiphenyl CompoundsHumansHydrogen BondingInhibitory Concentration 50Molecular StructureNicotinic AntagonistsQuantitative Structure-Activity RelationshipReceptors, NicotinicBiphenyl CompoundsCOB-172COB-175Nicotinic Antagonistsnicotinic receptor alpha3beta4nicotinic receptor alpha4beta2Receptors, Nicotinic

Identifiers

PMID22285942
PMCPMC3274641
OpenAlexW2001313740

What OpenQuestion holds

Textmetadata
LicenceTDM
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.