Harnessing the Anti-Nociceptive Potential of NK2 and NK3 Ligands in the Design of New Multifunctional μ/δ-Opioid Agonist-Neurokinin Antagonist Peptidomimetics.

Charlène Gadais, Justyna Piekielna-Ciesielska, Jolien De Neve, Charlotte Martin, Anna Janecka, Steven Ballet

Open access · goldAbstract read

In one paragraph

Article in Molecules (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it

0cells of the map it votes in

2citing papers in PubMed

0.9field-weighted citation impact, top 30% 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

2 citing papers in PubMed, 11 citations in OpenAlex.

Design, Synthesis, andACS pharmacology & translational science · 2024
Article
Phylogenetic Analysis Provides Insight Into the Molecular Evolution of Nociception and Pain-Related Proteins.Evolutionary bioinformatics online · 2023
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 3 countries.

Charlène GadaisResearch Group of Organic Chemistry, Departments of Bioengineering Sciences and Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.ORCID 0000-0002-6061-0420

Justyna Piekielna-CiesielskaDepartment of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland.

Jolien De NeveResearch Group of Organic Chemistry, Departments of Bioengineering Sciences and Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.

Charlotte MartinResearch Group of Organic Chemistry, Departments of Bioengineering Sciences and Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.

Anna JaneckaDepartment of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland.

Steven BalletResearch Group of Organic Chemistry, Departments of Bioengineering Sciences and Chemistry, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium.

Vrije Universiteit Brussel · BEMedical University of Lodz · PL

Funding

Vrije Universiteit Brussel SRP50

6 · The paper itself

Abstract

Opioid agonists are well-established analgesics, widely prescribed for acute but also chronic pain. However, their efficiency comes with the price of drastically impacting side effects that are inherently linked to their prolonged use. To answer these liabilities, designed multiple ligands (DMLs) offer a promising strategy by co-targeting opioid and non-opioid signaling pathways involved in nociception. Despite being intimately linked to the Substance P (SP)/neurokinin 1 (NK1) system, which is broadly examined for pain treatment, the neurokinin receptors NK2 and NK3 have so far been neglected in such DMLs. Herein, a series of newly designed opioid agonist-NK2 or -NK3 antagonists is reported. A selection of reported peptidic, pseudo-peptidic, and non-peptide neurokinin NK2 and NK3 ligands were covalently linked to the peptidic μ-opioid selective pharmacophore Dmt-DALDA (H-Dmt-d-Arg-Phe-Lys-NH

Indexed as

Amino Acid SequenceAnalgesics, OpioidHumansLigandsNeurokinin-1 Receptor AntagonistsOligopeptidesPeptidomimeticsProtein BindingProtein ConformationReceptors, Neurokinin-1Receptors, Opioid, muStructure-Activity RelationshipSubstance PAnalgesics, OpioidLigandsNeurokinin-1 Receptor AntagonistsOligopeptidesPeptidomimeticsReceptors, Neurokinin-1Receptors, Opioid, muSubstance Ptyrosyl-arginyl-phenylalanyl-lysinamideantinociceptiondesigned multiple ligandneurokininNK2NK3opioid agonistpeptidepeptidomimeticsδ-opioid receptorμ-opioid receptor

Identifiers

PMID34500841

DOI10.3390/molecules26175406

PMCPMC8434392

OpenAlexW3197591732

What Socratic holds

Textmetadata

LicenceCC BY

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 Socratic graph.