Evidence map›Paper›PMID 40643363›Full record

ArticleJournal of medicinal chemistry2025

Discovery of the First Highly Selective 1,4-dihydropyrido[3,4-

Leon Katzengruber, Pascal Sander, Stefan Zwirner, Alexander Rasch, Eric Eberlein, Roland Selig, Wolfgang Albrecht, Lars Zender, Stefan A Laufer

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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

9 authors.

Leon KatzengruberDepartment of Pharmaceutical/Medicinal Chemistry, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen 72076, Germany.
Pascal SanderDepartment of Pharmaceutical/Medicinal Chemistry, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen 72076, Germany.
Stefan ZwirnerDepartment of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tübingen,, Tübingen 72076, Germany.
Alexander RaschDepartment of Pharmaceutical/Medicinal Chemistry, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen 72076, Germany.
Eric EberleinDepartment of Pharmaceutical/Medicinal Chemistry, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen 72076, Germany.ORCID 0009-0006-0010-2738
Roland SeligDepartment of Pharmaceutical/Medicinal Chemistry, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen 72076, Germany.
Wolfgang AlbrechtHepaRegenix GmbH, Eisenbahnstraße 63, Tübingen 72072, Germany.
Lars ZenderDepartment of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tübingen,, Tübingen 72076, Germany.
Stefan A LauferDepartment of Pharmaceutical/Medicinal Chemistry, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, Tübingen 72076, Germany.ORCID 0000-0001-6952-1486

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Due to limited treatment options, liver failure remains a major challenge in modern medicine. With the validation of mitogen-activated protein kinase kinase 4 (MKK4, also known as MEK4 or MAP2K4) as a regulator of hepatocyte regeneration, a promising target for curative treatment of degenerative liver diseases was recently identified via in vivo RNAi experiments. The field of small molecules targeting MKK4 is of growing interest. Several MKK4 inhibitors with differing scaffolds are known, but few have reasonable selectivity profiles and drug-like properties. To further explore the space of drug-like MKK4 scaffolds, we performed a broad screening campaign and identified BI-D1870 as a promising candidate. The dihydropteridinone BI-D1870 is an unselective ribosomal S6 kinase inhibitor with broad off-target activity. In the study presented herein, we report a successful off-to-on target strategy that led to the development of highly selective 1,4-dihydropyrido[3,4-

Indexed as

Drug DiscoveryMAP Kinase Kinase 4Protein Kinase InhibitorsPyrazinesAnimalsHumansStructure-Activity RelationshipMAP Kinase Kinase 4Protein Kinase InhibitorsPyrazines

Identifiers

PMID40643363
PMCPMC12305495

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.