Evidence map›Paper›PMID 27435185›Full record

ArticleJournal of enzyme inhibition and medicinal chemistry2016

Furoates and thenoates inhibit pyruvate dehydrogenase kinase 2 allosterically by binding to its pyruvate regulatory site.

Tiziana Masini, Barbara Birkaya, Simon van Dijk, Milon Mondal, Johan Hekelaar, Manuel Jäger, Anke C Terwisscha van Scheltinga, Mulchand S Patel, Anna K H Hirsch, Edelmiro Moman

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

Article in Journal of enzyme inhibition and medicinal chemistry, 2016. 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
0.5field-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

3 citing papers in PubMed, 7 citations in OpenAlex.

  1. Review
  2. Review
  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

10 authors at 3 institutions in 3 countries.

Tiziana Masinia Stratingh Institute for Chemistry, University of Groningen , Groningen , The Netherlands.
Barbara Birkayab Department of Biochemistry , School of Medicine and Biomedical Sciences, University at Buffalo, the State University of New York , Buffalo , NY , USA.
Simon van Dijka Stratingh Institute for Chemistry, University of Groningen , Groningen , The Netherlands.
Milon Mondala Stratingh Institute for Chemistry, University of Groningen , Groningen , The Netherlands.
Johan Hekelaarc Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen , Groningen , The Netherlands.
Manuel Jägera Stratingh Institute for Chemistry, University of Groningen , Groningen , The Netherlands.
Anke C Terwisscha van Scheltingac Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen , Groningen , The Netherlands.
Mulchand S Patelb Department of Biochemistry , School of Medicine and Biomedical Sciences, University at Buffalo, the State University of New York , Buffalo , NY , USA.
Anna K H Hirscha Stratingh Institute for Chemistry, University of Groningen , Groningen , The Netherlands.
Edelmiro Momand Molecular Design Group, Trinity Biomedical Sciences Institute, Trinity College Dublin , Dublin , Ireland , and.
University of Groningen · NLUniversity at Buffalo, State University of New York · USTrinity College Dublin · IE

Funding

Mechanism and Molecular Recognition in Human Pyruvate Dehydrogenase ComplexR56DK080748 · NIDDK · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI PATEL, MULCHAND S · 2008 to 2008
$198k
NIDDK NIH HHS R56 DK080748
6 · The paper itself

Abstract

The last decade has witnessed the reawakening of cancer metabolism as a therapeutic target. In particular, inhibition of pyruvate dehydrogenase kinase (PDK) holds remarkable promise. Dichloroacetic acid (DCA), currently undergoing clinical trials, is a unique PDK inhibitor in which it binds to the allosteric pyruvate site of the enzyme. However, the safety of DCA as a drug is compromised by its neurotoxicity, whereas its usefulness as an investigative tool is limited by the high concentrations required to exert observable effects in cell culture. Herein, we report the identification - by making use of saturation-transfer difference NMR spectroscopy, enzymatic assays and computational methods - of furoate and thenoate derivatives as allosteric pyruvate-site-binding PDK2 inhibitors. This work substantiates the pyruvate regulatory pocket as a druggable target.

Indexed as

Allosteric RegulationAllosteric SiteDose-Response Relationship, DrugFuransHumansMolecular StructureProtein Kinase InhibitorsProtein Serine-Threonine KinasesPyruvate Dehydrogenase Acetyl-Transferring KinasePyruvic AcidStructure-Activity RelationshipThiophenesFuransPDK2 protein, humanProtein Kinase InhibitorsProtein Serine-Threonine KinasesPyruvate Dehydrogenase Acetyl-Transferring KinasePyruvic AcidThiophenesCancer metabolismDCAdichloroacetatePDCPDK2 inhibitorspyruvate

Identifiers

PMID27435185
PMCPMC5553292
OpenAlexW2480416583

What OpenQuestion holds

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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.