Evidence map›Paper›PMID 37093023›Full record

ArticleAntimicrobial agents and chemotherapy2023

The Novel DNA Binding Mechanism of Ridinilazole, a Precision

Clive S Mason, Tim Avis, Chenlin Hu, Nabeetha Nagalingam, Manikhandan Mudaliar, Chris Coward, Khurshida Begum, Kathleen Gajewski, M Jahangir Alam, Eugenie Bassères and 6 more

Open access · hybridAbstract read
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
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

9 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025
    Review
  7. Review
  8. Article
  9. 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

16 authors at 4 institutions in 2 countries.

Clive S MasonSummit Therapeutics, Cambridge, United Kingdom.ORCID 0000-0003-3179-6622
Tim AvisSummit Therapeutics, Cambridge, United Kingdom.
Chenlin HuDepartment of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA.
Nabeetha NagalingamSummit Therapeutics, Cambridge, United Kingdom.
Manikhandan MudaliarSummit Therapeutics, Cambridge, United Kingdom.
Chris CowardSummit Therapeutics, Cambridge, United Kingdom.
Khurshida BegumDepartment of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA.
Kathleen GajewskiDepartment of Biology & Biochemistry, University of Houston Colleges of Natural Sciences and Mathematics, Houston, Texas, USA.
M Jahangir AlamDepartment of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA.
Eugenie BassèresDepartment of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA.
Stephen MossDomainex Ltd., Cambridge, United Kingdom.
Stefanie ReichDomainex Ltd., Cambridge, United Kingdom.
Esther DuperchySummit Therapeutics, Abingdon, United Kingdom.
Keith R FoxSchool of Biological Sciences, University of Southampton, Southampton, United Kingdom.
Kevin W GareyDepartment of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA.
David J PowellSummit Therapeutics, Abingdon, United Kingdom.
Summit (United Kingdom) · GBUniversity of Houston · USDomainex (United Kingdom) · GBUniversity of Southampton · GB

Funding

Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9M
BD Biosciences Special Order LSRIIS10RR024574 · NCRR · BAYLOR COLLEGE OF MEDICINE · PI LUMPKIN, ELLEN A · 2009 to 2009
$430k
Olympus FV3000 Confocal Microscope for the Biology and Biochemistry Imaging Core Facility at the University of HoustonS10OD026827 · OD · UNIVERSITY OF HOUSTON · PI LEKVEN, ARNE C · 2020 to 2020
$359k
NCI NIH HHS P30 CA125123NCRR NIH HHS S10 RR024574NIH HHS S10 OD026827
6 · The paper itself

Abstract

Clostridioides difficile infection (CDI) causes substantial morbidity and mortality worldwide with limited antibiotic treatment options. Ridinilazole is a precision bisbenzimidazole antibiotic being developed to treat CDI and reduce unacceptably high rates of infection recurrence in patients. Although in late clinical development, the precise mechanism of action by which ridinilazole elicits its bactericidal activity has remained elusive. Here, we present conclusive biochemical and structural data to demonstrate that ridinilazole has a primary DNA binding mechanism, with a co-complex structure confirming binding to the DNA minor groove. Additional RNA-seq data indicated early pleiotropic changes to transcription, with broad effects on multiple C. difficile compartments and significant effects on energy generation pathways particularly. DNA binding and genomic localization was confirmed through confocal microscopy utilizing the intrinsic fluorescence of ridinilazole upon DNA binding. As such, ridinilazole has the potential to be the first antibiotic approved with a DNA minor groove binding mechanism of action.

Indexed as

Clostridioides difficileClostridium InfectionsAnti-Bacterial AgentsBenzimidazolesHumansPyridinesAnti-Bacterial AgentsBenzimidazolesPyridinesridinilazoleantibioticClostridium difficilemechanisms of action

Identifiers

PMID37093023
PMCPMC10246881
OpenAlexW4366821861

What OpenQuestion 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 OpenQuestion graph.