Evidence map›Paper›PMID 30316633›Full record

ArticleBioorganic & medicinal chemistry letters2018

Discovery of heterocyclic replacements for the coumarin core of anti-tubercular FadD32 inhibitors.

Chao Fang, Katie K Lee, Raymond Nietupski, Robert H Bates, Raquel Fernandez-Menendez, Eva Maria Lopez-Roman, Laura Guijarro-Lopez, Yunxing Yin, Zuozhong Peng, James E Gomez and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing 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

10 citing papers in PubMed.

  1. Article
  2. Review
  3. MedComm · 2023
    Review
  4. OvercomingActa pharmaceutica Sinica. B · 2022
    Review
  5. In Silico Drug Repurposing Approach: Investigation ofMolecules (Basel, Switzerland) · 2022
    Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. 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

15 authors.

Chao FangThe Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA.
Katie K LeeThe Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA; Department of Molecular Biology and Center for Integrative and Computational Biology, Massachusetts General Hospital, 185 Cambridge St, Boston, MA 02114, USA.
Raymond NietupskiThe Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA.
Robert H BatesDiseases of the Developing World, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Raquel Fernandez-MenendezDiseases of the Developing World, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Eva Maria Lopez-RomanDiseases of the Developing World, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Laura Guijarro-LopezDiseases of the Developing World, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Yunxing YinWuXi AppTec, 168 Nanhai Rd, Tianjin Economic-Technological Development Area (TEDA), Tianjin 300457, China.
Zuozhong PengWuXi AppTec, 288 Fute Zhong Rd, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
James E GomezThe Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA; Department of Molecular Biology and Center for Integrative and Computational Biology, Massachusetts General Hospital, 185 Cambridge St, Boston, MA 02114, USA.
Stewart FisherThe Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA.
David Barros-AguirreDiseases of the Developing World, GlaxoSmithKline, Severo Ochoa 2, Tres Cantos, 28760 Madrid, Spain.
Brian K HubbardThe Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA.
Michael H Serrano-WuThe Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA.
Deborah T HungThe Broad Institute of MIT and Harvard, 415 Main St, Cambridge, MA 02142, USA; Department of Molecular Biology and Center for Integrative and Computational Biology, Massachusetts General Hospital, 185 Cambridge St, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. Electronic address: hung@molbio.mgh.harvard.edu.

Funding

New targets against tuberculosisR01AI132300 · NIAID · BROAD INSTITUTE, INC. · PI HUNG, DEBORAH T · 2017 to 2021
$5.9M
NIAID NIH HHS R01 AI132300
6 · The paper itself

Abstract

Previous work established a coumarin scaffold as a starting point for inhibition of Mycobacterium tuberculosis (Mtb) FadD32 enzymatic activity. After further profiling of the coumarin inhibitor 4 revealed chemical instability, we discovered that a quinoline ring circumvented this instability and had the advantage of offering additional substitution vectors to further optimize. Ensuing SAR studies gave rise to quinoline-2-carboxamides with potent anti-tubercular activity. Further optimization of ADME/PK properties culminated in 21b that exhibited compelling in vivo efficacy in a mouse model of Mtb infection.

Indexed as

AnimalsAntitubercular AgentsBacterial ProteinsCoumarinsDisease Models, AnimalDrug Evaluation, PreclinicalMiceMicrobial Sensitivity TestsMycobacterium tuberculosisQuinolinesStructure-Activity RelationshipTuberculosisAntitubercular AgentsBacterial ProteinscoumarinCoumarinsquinolineQuinolinesFadD32 inhibitorIn vivo efficacyMycobacterium tuberculosisQuinoline-2-carboxamideStructure-activity relationship

Identifiers

PMID30316633
PMCPMC6233306

What OpenQuestion holds

Textmetadata
LicenceTDM
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.