Evidence map›Paper›PMID 39541507›Full record

ArticleJournal of medicinal chemistry2025

Discovery and Preclinical Characterization of Fulacimstat (BAY 1142524), a Potent and Selective Chymase Inhibitor As a New Profibrinolytic Approach for Safe Thrombus Resolution.

Chantal Fürstner, Jens Ackerstaff, Heinrich Meier, Alexander Straub, Joachim Mittendorf, Jens Schamberger, Martina Schäfer, Kirsten Börngen, Hannah Jörißen, Dmitry Zubov and 10 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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

20 authors.

Chantal FürstnerBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.ORCID 0000-0001-7370-5341
Jens AckerstaffBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Heinrich MeierBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Alexander StraubBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Joachim MittendorfBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Jens SchambergerBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Martina SchäferBayer AG, Pharmaceuticals, Research and Development, Müllerstrasse 178, 13353 Berlin, Germany.
Kirsten BörngenBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Hannah JörißenBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Dmitry ZubovBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Katja ZimmermannBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Adrian TersteegenBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Volker GeissBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Elke HartmannBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Barbara Albrecht-KüpperBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Pedro D'Orléans-JusteDepartment of Pharmacology and Physiology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.
Catherine LapointeDepartment of Pharmacology and Physiology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.
Laurence VincentDepartment of Pharmacology and Physiology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.
Stefan HeitmeierBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.
Hanna TinelBayer AG, Pharmaceuticals, Research and Development, Aprather Weg 18a, 42113 Wuppertal, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chymase is a serine-protease produced by mast cells. In the past few decades, its role in fibrotic diseases triggered the search for orally available chymase inhibitors. Aiming at reducing adverse cardiac remodeling after myocardial infarction, our research efforts resulted in the discovery of fulacimstat (BAY 1142524). While clinical trials did not demonstrate efficacy in this indication, the recent discovery of a new unexpected biological role of chymase spurred a revival of interest in chymase inhibition: chymase was shown to inactivate plasmin within fibrin-rich clots. Chymase inhibitors are now considered as potential profibrinolytic drugs with low bleeding risk and therefore exceptional safety for the treatment of acute thrombosis settings such as stroke, pulmonary embolism, or venous thrombosis. This article describes the chemical optimization journey from a screening hit to the discovery of fulacimstat (BAY 1142524), a selective chymase inhibitor with a good safety profile, as well as its preclinical

Indexed as

ChymasesThrombosisAnimalsDrug DiscoveryDrug Evaluation, PreclinicalFibrinolytic AgentsHumansMaleMiceRatsStructure-Activity RelationshipChymasesFibrinolytic Agents

Identifiers

PMID39541507
PMCPMC11956016

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.