Evidence map›Paper›PMID 25193297›Full record

ArticleEuropean journal of medicinal chemistry2014

Michael acceptor approach to the design of new salvinorin A-based high affinity ligands for the kappa-opioid receptor.

Prabhakar R Polepally, Krzysztof Huben, Eyal Vardy, Vincent Setola, Philip D Mosier, Bryan L Roth, Jordan K Zjawiony

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

Article in European journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.1field-weighted citation impact, top 15% 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

13 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Synthetic Studies of Neoclerodane Diterpenes fromACS chemical neuroscience · 2020
    Article
  8. Review
  9. A review of salvinorin analogs and their kappa-opioid receptor activity.Bioorganic & medicinal chemistry letters · 2018
    Review
  10. Article
  11. Review
  12. Article
  13. 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

7 authors at 3 institutions in 2 countries.

Prabhakar R PolepallyDepartment of BioMolecular Sciences, Division of Pharmacognosy, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA.
Krzysztof HubenDepartment of BioMolecular Sciences, Division of Pharmacognosy, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA; Institute of Organic Chemistry, Technical University of Lodz, 90-924 Lodz, Poland.
Eyal VardyDepartment of Pharmacology, Division of Chemical Biology and Medicinal Chemistry, Medical School, NIMH Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, NC 27599, USA.
Vincent SetolaDepartment of Pharmacology, Division of Chemical Biology and Medicinal Chemistry, Medical School, NIMH Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, NC 27599, USA.
Philip D MosierDepartment of Medicinal Chemistry and Institute for Structural Biology and Drug Discovery, Virginia Commonwealth University, Richmond, VA 23298-0540, USA.
Bryan L RothDepartment of Pharmacology, Division of Chemical Biology and Medicinal Chemistry, Medical School, NIMH Psychoactive Drug Screening Program, University of North Carolina, Chapel Hill, NC 27599, USA.
Jordan K ZjawionyDepartment of BioMolecular Sciences, Division of Pharmacognosy, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677-1848, USA. Electronic address: jordan@olemiss.edu.
University of Mississippi · USUniversity of North Carolina at Chapel Hill · USVirginia Commonwealth University · US

Funding

Diterpines as Selective Kappa Opioid Receptor AgonistsR01DA017204 · NIDA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROTH, BRYAN L. · 2003 to 2014
$3.2M
NIDA NIH HHS R01 DA017204NIMH NIH HHS HHSN271201300017CPHS HHS HHSN-271-2013-00017-C
6 · The paper itself

Abstract

The neoclerodane diterpenoid salvinorin A is a major secondary metabolite isolated from the psychoactive plant Salvia divinorum. Salvinorin A has been shown to have high affinity and selectivity for the κ-opioid receptor (KOR). To study the ligand-receptor interactions that occur between salvinorin A and the KOR, a new series of salvinorin A derivatives bearing potentially reactive Michael acceptor functional groups at C-2 was synthesized and used to probe the salvinorin A binding site. The κ-, δ-, and μ-opioid receptor (KOR, DOR and MOR, respectively) binding affinities and KOR efficacies were measured for the new compounds. Although none showed wash-resistant irreversible binding, most of them showed high affinity for the KOR, and some exhibited dual affinity to KOR and MOR. Molecular modeling techniques based on the recently-determined crystal structure of the KOR combined with results from mutagenesis studies, competitive binding, functional assays and structure-activity relationships, and previous salvinorin A-KOR interaction models were used to identify putative interaction modes of the new compounds with the KOR and MOR.

Indexed as

Drug DesignDiterpenes, ClerodaneHEK293 CellsHumansLigandsModels, MolecularProtein BindingProtein ConformationReceptors, Opioid, kappaDiterpenes, ClerodaneLigandsReceptors, Opioid, kappasalvinorin AKappa, delta, and mu opioid receptorsMichael acceptor-type ligandsMolecular modelingSalvinorin A and B

Identifiers

PMID25193297
PMCPMC4162805
OpenAlexW2017434974

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.