Evidence map›Paper›PMID 33590767›Full record

ArticleFuture medicinal chemistry2021

Exploring the putative mechanism of allosteric modulations by mixed-action kappa/mu opioid receptor bitopic modulators.

Huiqun Wang, Danni Cao, James C Gillespie, Rolando E Mendez, Dana E Selley, Lee-Yuan Liu-Chen, Yan Zhang

Abstract read
In one paragraph

Article in Future medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
  2. Article
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  5. Review
  6. Review
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

7 authors.

Huiqun WangDepartment of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0003-3105-2068
Danni CaoCenter for Substance Abuse Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
James C GillespieDepartment of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0002-7237-4568
Rolando E MendezDepartment of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0003-3335-2347
Dana E SelleyDepartment of Pharmacology & Toxicology, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0003-3118-9339
Lee-Yuan Liu-ChenCenter for Substance Abuse Research, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.ORCID 0000-0001-5206-9497
Yan ZhangDepartment of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.ORCID 0000-0001-8934-7016

Funding

Pilot Projects Core (PPC)P30DA013429 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI SCOTT M. RAWLS · 2000 to 2026
$34.6M
Mu Opioid Receptor Modulator Development to Treat Opioid Use DisorderUH3DA050311 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI ZHANG, YAN · 2023 to 2025
$4.3M
Non-peptide Mu Opioid Receptor Selective AntagonistsR01DA024022 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI ZHANG, YAN · 2009 to 2019
$3.5M
Pharmacology of Kappa Opioid ReceptorR01DA041359 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI LIU-CHEN, LEE-YUAN · 2017 to 2021
$2.9M
Bivalent Ligands as Chemical Probes to Study Opioid Abuse-enhanced HIV InfectionR01DA044855 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI HAUSER, KURT F, ZHANG, YAN · 2017 to 2021
$2.7M
Novel fentanyl derivatives as counteracting agents against fentanylUG3DA050311 · NIDA · VIRGINIA COMMONWEALTH UNIVERSITY · PI ZHANG, YAN · 2019 to 2020
$2.2M
Kappa opioid receptor in claustrumR21DA045274 · NIDA · TEMPLE UNIV OF THE COMMONWEALTH · PI LIU-CHEN, LEE-YUAN · 2018 to 2019
$436k
NIDA NIH HHS P30 DA013429NIDA NIH HHS R01 DA024022NIDA NIH HHS R01 DA041359NIDA NIH HHS R01 DA044855NIDA NIH HHS R21 DA045274NIDA NIH HHS UG3 DA050311NIDA NIH HHS UH3 DA050311
6 · The paper itself

Abstract

The modulation and selectivity mechanisms of seven mixed-action kappa opioid receptor (KOR)/mu opioid receptor (MOR) bitopic modulators were explored. Molecular modeling results indicated that the 'message' moiety of seven bitopic modulators shared the same binding mode with the orthosteric site of the KOR and MOR, whereas the 'address' moiety bound with different subdomains of the allosteric site of the KOR and MOR. The 'address' moiety of seven bitopic modulators bound to different subdomains of the allosteric site of the KOR and MOR may exhibit distinguishable allosteric modulations to the binding affinity and/or efficacy of the 'message' moiety. Moreover, the 3-hydroxy group on the phenolic moiety of the seven bitopic modulators induced selectivity to the KOR over the MOR.

Indexed as

Allosteric RegulationAllosteric SiteBinding SitesHumansLigandsMolecular Docking SimulationMorphinansNaltrexoneProtein BindingReceptors, Opioid, kappaReceptors, Opioid, muSpiro CompoundsThermodynamicsbeta-funaltrexamineLigandsMorphinansNaltrexoneReceptors, Opioid, kappaReceptors, Opioid, muSpiro CompoundsTRK 820allosteric modulation mechanismkappa opioid receptor (KOR)/mu opioid receptor (MOR)mixed-action KOR/MOR ligandmolecular dynamics simulationspsychostimulant abuse and addictionselectivity

Identifiers

PMID33590767
PMCPMC8027703

What OpenQuestion holds

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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 OpenQuestion graph.