Evidence map›Paper›PMID 24001138›Full record

ArticleBioscience reports2013

Ciprofloxacin is an inhibitor of the Mcm2-7 replicative helicase.

Nicholas Simon, Matthew L Bochman, Sandlin Seguin, Jeffrey L Brodsky, William L Seibel, Anthony Schwacha

Open access · goldAbstract read
In one paragraph

Article in Bioscience reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

35 citing papers in PubMed, 51 citations in OpenAlex.

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  8. RSC advances · 2022
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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

6 authors at 1 institution in 1 country.

Nicholas Simon*Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, U.S.A.
Matthew L Bochman
Sandlin Seguin*Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, U.S.A.
Jeffrey L Brodsky*Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, U.S.A.
William L Seibel†Drug Discovery Center, University of Cincinnati, Cincinnati, OH 45237, U.S.A.
Anthony Schwacha*Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, U.S.A.
University of Pittsburgh · US

Funding

University of Pittsburgh Center for Chemical DiversityP50GM067082 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI WIPF, PETER · 2002 to 2012
$18.6M
Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
The Role of the MCM2-7 Complex in the Replication Fork ProcessivityR01GM083985 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SCHWACHA, ANTHONY · 2009 to 2013
$1.3M
NIDDK NIH HHS P30 DK079307NIDDK NIH HHS P30 DK79307NIGMS NIH HHS 1R01GM83985-1A1NIGMS NIH HHS P50 GM067082
6 · The paper itself

Abstract

Most currently available small molecule inhibitors of DNA replication lack enzymatic specificity, resulting in deleterious side effects during use in cancer chemotherapy and limited experimental usefulness as mechanistic tools to study DNA replication. Towards development of targeted replication inhibitors, we have focused on Mcm2-7 (minichromosome maintenance protein 2-7), a highly conserved helicase and key regulatory component of eukaryotic DNA replication. Unexpectedly we found that the fluoroquinolone antibiotic ciprofloxacin preferentially inhibits Mcm2-7. Ciprofloxacin blocks the DNA helicase activity of Mcm2-7 at concentrations that have little effect on other tested helicases and prevents the proliferation of both yeast and human cells at concentrations similar to those that inhibit DNA unwinding. Moreover, a previously characterized mcm mutant (mcm4chaos3) exhibits increased ciprofloxacin resistance. To identify more potent Mcm2-7 inhibitors, we screened molecules that are structurally related to ciprofloxacin and identified several that compromise the Mcm2-7 helicase activity at lower concentrations. Our results indicate that ciprofloxacin targets Mcm2-7 in vitro, and support the feasibility of developing specific quinolone-based inhibitors of Mcm2-7 for therapeutic and experimental applications.

Indexed as

AnimalsAntibiotics, AntineoplasticCell LineCiprofloxacinDrug Resistance, NeoplasmDrug Screening Assays, AntitumorHumansInhibitory Concentration 50Minichromosome Maintenance ProteinsOfloxacinSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsAntibiotics, AntineoplasticCiprofloxacinMinichromosome Maintenance ProteinsOfloxacinSaccharomyces cerevisiae Proteins

Identifiers

PMID24001138
PMCPMC3791872
OpenAlexW1973337866

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.