Evidence map›Paper›PMID 42089702›Full record

ArticleJournal of medicinal chemistry2026

Darizmetinib (HRX215): A Promising 1st-in-Class Liver Regenerating Drug in Phase 1b/2a Clinical Development, Targeting the Stress Signaling Protein Kinase MKK4.

Wolfgang Albrecht, Roland Selig, Bent Pfaffenrot, Philip Kloevekorn, Michael Juchum, Stefan Zwirner, Sabrina Klotz, Lars Zender, Stefan Laufer

Abstract read
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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. 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. 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

9 authors.

Wolfgang AlbrechtHepaRegeniX GmbH, Tuebingen 72072, Germany.
Roland SeligHepaRegeniX GmbH, Tuebingen 72072, Germany.
Bent PfaffenrotDepartment of Pharmaceutical Chemistry, University of Tuebingen, Tuebingen 72076, Germany.
Philip KloevekornDepartment of Pharmaceutical Chemistry, University of Tuebingen, Tuebingen 72076, Germany.
Michael JuchumDepartment of Pharmaceutical Chemistry, University of Tuebingen, Tuebingen 72076, Germany.
Stefan ZwirnerHepaRegeniX GmbH, Tuebingen 72072, Germany.
Sabrina KlotzDepartment of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen 72076, Germany.
Lars ZenderDepartment of Medical Oncology and Pneumology (Internal Medicine VIII), University Hospital Tuebingen, Tuebingen 72076, Germany.
Stefan LauferDepartment of Pharmaceutical Chemistry, University of Tuebingen, Tuebingen 72076, Germany.ORCID 0000-0001-6952-1486

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mitogen-activated protein kinase kinase 4 (MKK4), a MAP2 kinase that activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase, is a key kinase of the stress-activated protein kinase (SAPK)/mitogen-activated protein kinase (MAPK) signaling network. Inhibition of MKK4 represents a novel therapeutic approach by leveraging a rerouting mechanism within the signaling network, predominantly via MKK7 and JNK1, to modulate the regenerative capacity of hepatocytes. In this study, we describe the discovery of darizmetinib (HRX215), a first-in-class MKK4 inhibitor currently in clinical development. Darizmetinib was derived from a known BRaf inhibitor, and through extensive structure-activity relationship (SAR) studies, we successfully engineered potency and selectivity for MKK4 while eliminating the original BRaf on-target activity. Preclinical proof-of-concept studies, along with

Indexed as

Liver RegenerationMAP Kinase Kinase 4Protein Kinase InhibitorsAnimalsHumansMaleMiceStructure-Activity RelationshipMAP2K4 protein, humanMAP Kinase Kinase 4Protein Kinase Inhibitors

Identifiers

PMID42089702
PMCPMC13224088

What OpenQuestion holds

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Registered trials

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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.