Evidence map›Paper›PMID 36050506›Full record

ArticleScientific reports2022

Novel chemical entities inhibiting Mycobacterium tuberculosis growth identified by phenotypic high-throughput screening.

Anuradha Kumar, Somsundaram Chettiar, Brian S Brown, Julie Early, Juliane Ollinger, Megan Files, Mai A Bailey, Aaron Korkegian, Devon Dennison, Matthew McNeil and 8 more

Abstract read
In one paragraph

Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

18 authors.

Anuradha KumarInfectious Disease Research Institute, Seattle, WA, 98102, USA.
Somsundaram ChettiarInfectious Disease Research Institute, Seattle, WA, 98102, USA.
Brian S BrownAbbVie Inc., North Chicago, IL, USA.
Julie EarlyInfectious Disease Research Institute, Seattle, WA, 98102, USA.
Juliane OllingerInfectious Disease Research Institute, Seattle, WA, 98102, USA.
Megan FilesInfectious Disease Research Institute, Seattle, WA, 98102, USA.
Mai A BaileyInfectious Disease Research Institute, Seattle, WA, 98102, USA.
Aaron KorkegianInfectious Disease Research Institute, Seattle, WA, 98102, USA.
Devon DennisonInfectious Disease Research Institute, Seattle, WA, 98102, USA.
Matthew McNeilInfectious Disease Research Institute, Seattle, WA, 98102, USA.
James MetzAbbVie Inc., North Chicago, IL, USA.
Augustine OsumaAbbVie Inc., North Chicago, IL, USA.
Michael CurtinAbbVie Inc., North Chicago, IL, USA.
Aaron KunzerAbbVie Inc., North Chicago, IL, USA.
Gail FreibergAbbVie Inc., North Chicago, IL, USA.
Milan BrunckoAbbVie Inc., North Chicago, IL, USA.
Dale KempfAbbVie Inc., North Chicago, IL, USA.
Tanya ParishInfectious Disease Research Institute, Seattle, WA, 98102, USA. tanya.parish@seattlechildrens.org.

Funding

Bill & Melinda Gates Foundation OPP1024038
6 · The paper itself

Abstract

We performed a high-throughput phenotypic whole cell screen of Mycobacterium tuberculosis against a diverse chemical library of approximately 100,000 compounds from the AbbVie corporate collection and identified 24 chemotypes with anti-tubercular activity. We selected two series for further exploration and conducted structure-activity relationship studies with new analogs for the 4-phenyl piperidines (4PP) and phenylcyclobutane carboxamides (PCB). Strains with mutations in MmpL3 demonstrated resistance to both compound series. We isolated resistant mutants for the two series and found mutations in MmpL3. These data suggest that MmpL3 is the target, or mechanism of resistance for both series.

Indexed as

Mycobacterium tuberculosisAntitubercular AgentsBacterial ProteinsHigh-Throughput Screening AssaysMembrane Transport ProteinsMicrobial Sensitivity TestsAntitubercular AgentsBacterial ProteinsMembrane Transport Proteins

Identifiers

PMID36050506
PMCPMC9435431

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.