Evidence map›Paper›PMID 24440298›Full record

ArticleBioorganic & medicinal chemistry letters2014

Virtual screening reveals allosteric inhibitors of the Toxoplasma gondii thymidylate synthase-dihydrofolate reductase.

Hitesh Sharma, Mark J Landau, Todd J Sullivan, Vidya P Kumar, Markus K Dahlgren, William L Jorgensen, Karen S Anderson

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.3field-weighted citation impact, top 24% 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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Modeling enzyme-ligand binding in drug discovery.Journal of cheminformatics · 2015
    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

7 authors at 1 institution in 1 country.

Hitesh SharmaDepartment of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Mark J LandauDepartment of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Todd J SullivanDepartment of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA.
Vidya P KumarDepartment of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Markus K DahlgrenDepartment of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA.
William L JorgensenDepartment of Chemistry, Yale University, 225 Prospect Street, New Haven, CT 06520, USA.
Karen S AndersonDepartment of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Molecular Biophysics & Biochemistry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: karen.anderson@yale.edu.
Yale University · US

Funding

POTENTIAL FUNCTIONS FOR WATER PROTEIN INTERACTIONSR01GM032136 · NIGMS · YALE UNIVERSITY · PI JORGENSEN, WILLIAM L. · 1985 to 2023
$8.2M
Predoc Training at the Interface Chemistry and BiologyT32GM067543 · NIGMS · YALE UNIVERSITY · PI CRAWFORD, JASON MICHAEL · 2003 to 2022
$7.4M
Exploring Novel Targeting Strategies for AIDS Protozoal PathogensR01AI083146 · NIAID · YALE UNIVERSITY · PI ANDERSON, KAREN S. · 2010 to 2019
$3.9M
Exploring Novel Targeting Strategies for AIDS Protozoal PathogensR56AI083146 · NIAID · YALE UNIVERSITY · PI ANDERSON, KAREN S. · 2009 to 2009
$414k
NIAID NIH HHS AI083146NIAID NIH HHS R01 AI083146NIAID NIH HHS R56 AI083146NIGMS NIH HHS 5 T32 GM067543NIGMS NIH HHS GM32136NIGMS NIH HHS R01 GM032136NIGMS NIH HHS T32 GM067543
6 · The paper itself

Abstract

The parasite Toxoplasma gondii can lead to toxoplasmosis in those who are immunocompromised. To combat the infection, the enzyme responsible for nucleotide synthesis thymidylate synthase-dihydrofolate reductase (TS-DHFR) is a suitable drug target. We have used virtual screening to determine novel allosteric inhibitors at the interface between the two TS domains. Selected compounds from virtual screening inhibited TS activity. Thus, these results show that allosteric inhibition by small drug-like molecules can occur in T. gondii TS-DHFR and pave the way for new and potent species-specific inhibitors.

Indexed as

Drug Evaluation, PreclinicalAllosteric RegulationDose-Response Relationship, DrugEnzyme InhibitorsModels, MolecularMolecular StructureMultienzyme ComplexesStructure-Activity RelationshipTetrahydrofolate DehydrogenaseThymidylate SynthaseToxoplasmaEnzyme InhibitorsMultienzyme ComplexesTetrahydrofolate DehydrogenaseThymidylate Synthasethymidylate synthase-dihydrofolate reductaseDihydrofolate reductaseThymidylate synthaseToxoplasma gondiiVirtual screening

Identifiers

PMID24440298
PMCPMC3946055
OpenAlexW2013433800

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.