Evidence map›Paper›PMID 42380264›Full record

Articlenpj drug discovery2025

Cystobactamid off-target profiling reveals favorable safety, superoxide reduction, and SCARB1 inhibition in eukaryotes.

Timo Risch, Benedikt Hellwinkel, Dietrich Mostert, Andreas M Kany, Danny Solga, Tim Seedorf, Dominik Heimann, Jessica Hoppstädter, Daniel Kohnhäuser, Jil-Sophie Hilgers and 9 more

Abstract read
In one paragraph

Article in npj drug discovery, 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. 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

19 authors.

Timo RischHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, PharmaScienceHub (PSH), Campus E8.1, 66123, Saarbrücken, Germany.
Benedikt HellwinkelTWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research and the Hannover Medical School, Hannover, Germany.
Dietrich MostertCenter for Functional Protein Assemblies (CPA), Department of Chemistry, Chair of Organic Chemistry II, Technical University of Munich, Ernst-Otto-Fischer-Straße 8, 85748, Garching, Germany.
Andreas M KanyHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, PharmaScienceHub (PSH), Campus E8.1, 66123, Saarbrücken, Germany.
Danny SolgaLeibniz University Hannover, Institute of Organic Chemistry, Schneiderberg 1B, 30167, Hannover, Germany.
Tim SeedorfLeibniz University Hannover, Institute of Organic Chemistry, Schneiderberg 1B, 30167, Hannover, Germany.
Dominik HeimannGerman Center for Infection Research (DZIF), Inhoffenstraße 7, 38124, Braunschweig, Germany.
Jessica HoppstädterDepartment of Pharmacy, Pharmaceutical Biology, Saarland University, PharmaScienceHub (PSH), Campus C2 3, 66123, Saarbruecken, Germany.
Daniel KohnhäuserGerman Center for Infection Research (DZIF), Inhoffenstraße 7, 38124, Braunschweig, Germany.
Jil-Sophie HilgersHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, PharmaScienceHub (PSH), Campus E8.1, 66123, Saarbrücken, Germany.
Franziska FriesHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, PharmaScienceHub (PSH), Campus E8.1, 66123, Saarbrücken, Germany.
Felix DeschnerHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, PharmaScienceHub (PSH), Campus E8.1, 66123, Saarbrücken, Germany.
Mark BrönstrupGerman Center for Infection Research (DZIF), Inhoffenstraße 7, 38124, Braunschweig, Germany.
Andreas KirschningLeibniz University Hannover, Institute of Organic Chemistry, Schneiderberg 1B, 30167, Hannover, Germany.
Stephan A SieberHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, PharmaScienceHub (PSH), Campus E8.1, 66123, Saarbrücken, Germany.
Thomas PietschmannGerman Center for Infection Research (DZIF), Inhoffenstraße 7, 38124, Braunschweig, Germany.
Alexandra K KiemerDepartment of Pharmacy, Pharmaceutical Biology, Saarland University, PharmaScienceHub (PSH), Campus C2 3, 66123, Saarbruecken, Germany.
Jennifer HerrmannHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, PharmaScienceHub (PSH), Campus E8.1, 66123, Saarbrücken, Germany. jennifer.herrmann@helmholtz-hips.de.
Rolf MüllerHelmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI), Saarland University, PharmaScienceHub (PSH), Campus E8.1, 66123, Saarbrücken, Germany. rolf.mueller@helmholtz-hips.de.

Funding

German Federal Ministry of Education and Research 16GW0219K
6 · The paper itself

Abstract

Antimicrobial resistance poses a fundamental global threat, necessitating new strategies for effective therapies. Cystobactamids, a class of antibacterial agents targeting bacterial gyrase and topoisomerase IV, represent a non-traditional chemical scaffold with broad-spectrum activity. For toxicological de-risking, we performed a comprehensive profiling on eukaryotic cells, focusing on cytotoxicity, genotoxicity, and mitochondrial toxicity, demonstrating cellular safety and superoxide scavenging properties. Studies in zebrafish embryos assessed developmental, cardiovascular, and hepatic toxicity, indicating a favorable in vivo safety profile. Metabolism studies revealed glucuronidation and amide bond hydrolysis as key pathways, whereby cystobactamid metabolic stability substantially improved by cobicistat co-treatment. Affinity-based protein profiling identified the cholesterol- and HCV-receptor scavenger receptor class B member 1 (SCARB1) as a primary eukaryotic off-target protein, with cystobactamids shown to inhibit SCARB1´s function, preventing hepatitis C virus pseudoparticle entry into cells. These findings suggest a high therapeutic potential for cystobactamids and highlight SCARB1 as a primary eukaryotic target.

Identifiers

PMID42380264
PMCPMC13267113

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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.