Evidence map›Paper›PMID 40404564›Full record

ArticleJournal of medicinal chemistry2025

A "Ligand First" Approach toward Selective, Covalent JNK2/3 Inhibitors.

Valentin R Wydra, Nicole Plank, Stefan Zwirner, Roland Selig, Alexander Rasch, Benedikt Masberg, Michael Lämmerhofer, Lars Zender, Pierre Koch, Wolfgang Albrecht and 1 more

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

11 authors.

Valentin R WydraDepartment of Pharmaceutical/Medicinal Chemistry, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, DE, Germany.ORCID 0009-0004-3295-0526
Nicole PlankDepartment of Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany.
Stefan ZwirnerDepartment of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital of Tübingen, Otfried-Müller-Straße 14, 72076 Tübingen, Germany.
Roland SeligDepartment of Pharmaceutical/Medicinal Chemistry, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, DE, Germany.
Alexander RaschDepartment of Pharmaceutical/Medicinal Chemistry, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, DE, Germany.
Benedikt MasbergPharmaceutical (Bio-) Analysis, Institute of Pharmaceutical Sciences, Department of Pharmaceutical/Medicinal Chemistry, Eberhard Karls Universität Tübingen, Tübingen 72076, Germany.ORCID 0000-0003-2041-4983
Michael LämmerhoferPharmaceutical (Bio-) Analysis, Institute of Pharmaceutical Sciences, Department of Pharmaceutical/Medicinal Chemistry, Eberhard Karls Universität Tübingen, Tübingen 72076, Germany.ORCID 0000-0002-1318-0974
Lars ZenderDepartment of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital of Tübingen, Otfried-Müller-Straße 14, 72076 Tübingen, Germany.
Pierre KochDepartment of Pharmaceutical/Medicinal Chemistry II, Institute of Pharmacy, University of Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany.ORCID 0000-0003-4620-4650
Wolfgang AlbrechtHepaRegenix GmbH, Eisenbahnstraße 63, 72072 Tübingen, Germany.
Stefan LauferDepartment of Pharmaceutical/Medicinal Chemistry, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, DE, Germany.ORCID 0000-0001-6952-1486

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

All JNK isoforms play a specific role in various diseases. The role of the JNK2 isoform has so far received little attention compared to its JNK1 and JNK3 counterparts with JNK3 being a potential target for neurodegenerative diseases and an inhibitor with JNK1 bias being currently investigated in clinical trials. Using an iterative, structure-guided optimization approach starting from a reported reversible binding aminopyrazole-derived scaffold, novel highly potent JNK2/3 selective inhibitors were generated ("ligand-first approach"). These reversible inhibitors were further transformed to covalent inhibitors by attaching an electrophilic warhead moiety, able to address a conserved cysteine side chain present in JNKs. Reversible and covalent inhibitors presented in this study show high JNK2/3 isoform selectivity and activity in cells. The covalently acting lead compound

Indexed as

Mitogen-Activated Protein Kinase 10Mitogen-Activated Protein Kinase 9Protein Kinase InhibitorsPyrazolesHumansLigandsModels, MolecularStructure-Activity RelationshipLigandsMitogen-Activated Protein Kinase 10Mitogen-Activated Protein Kinase 9Protein Kinase InhibitorsPyrazoles

Identifiers

PMID40404564
PMCPMC12169684

What OpenQuestion holds

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LicenceCC BY
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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.