Evidence map›Paper›PMID 41641864›Full record

ArticleJournal of medicinal chemistry2026

Mechanistic Insights into G Protein-Biased κ-Opioid Receptor Signaling Using Dual-Charged Naltrexamine Amides.

Niklas Piet Doering, Kristina Puls, Marta Diceglie, Anja Meraner, Axel Hentsch, Siriwat Hongnak, Armin Wurzer, Helmut Schmidhammer, Mariana Spetea, Marc Nazare and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

11 authors.

Niklas Piet DoeringDepartment of Biology, Chemistry and Pharmacy, Institute of Pharmacy, Molecular Design Group, Königin-Luise-Str. 2 + 4, Berlin 14195, Germany.ORCID 0009-0004-8238-2985
Kristina PulsDepartment of Biology, Chemistry and Pharmacy, Institute of Pharmacy, Molecular Design Group, Königin-Luise-Str. 2 + 4, Berlin 14195, Germany.
Marta DiceglieMedicinal Chemistry, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Campus Berlin Buch, Robert-Roessle-Str. 10, Berlin 13125, Germany.ORCID 0009-0002-2668-3631
Anja MeranerDepartment of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, Innsbruck 6020, Austria.
Axel HentschMedicinal Chemistry, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Campus Berlin Buch, Robert-Roessle-Str. 10, Berlin 13125, Germany.
Siriwat HongnakDepartment of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, Innsbruck 6020, Austria.ORCID 0009-0001-0981-2131
Armin WurzerDepartment of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, Innsbruck 6020, Austria.
Helmut SchmidhammerDepartment of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, Innsbruck 6020, Austria.ORCID 0000-0001-8752-5050
Mariana SpeteaDepartment of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI), University of Innsbruck, Innrain 80-82, Innsbruck 6020, Austria.ORCID 0000-0002-2379-5358
Marc NazareMedicinal Chemistry, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Campus Berlin Buch, Robert-Roessle-Str. 10, Berlin 13125, Germany.ORCID 0000-0002-1602-2330
Gerhard WolberDepartment of Biology, Chemistry and Pharmacy, Institute of Pharmacy, Molecular Design Group, Königin-Luise-Str. 2 + 4, Berlin 14195, Germany.ORCID 0000-0002-5344-0048

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Opioids remain a cornerstone of pain management, but currently used therapeutics are associated with serious side effects. While κ-opioid receptor (KOR) agonists offer an alternative to classical μ-opioid receptor (MOR) agonists, their clinical potential is limited by severe adverse effects. G protein-biased KOR agonists are a promising strategy for developing safer analgesics. In this study, we used virtual screening to develop novel dual-charged naltrexamine amide derivatives as tool compounds for investigating biased agonism at the KOR. All of the predicted ligands demonstrate low-nanomolar activity and G protein bias at both the KOR and MOR. Molecular dynamics simulations revealed a key allosteric communication involving TM4, TM5, and ICL2. These compounds achieve their effects through interactions with residues E209

Identifiers

PMID41641864
PMCPMC12951437

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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.