Evidence map›Paper›PMID 26746582›Full record

ArticleJournal of biomolecular screening2016

Human Adenine Nucleotide Translocase (ANT) Modulators Identified by High-Throughput Screening of Transgenic Yeast.

Yujian Zhang, Defeng Tian, Hironori Matsuyama, Takashi Hamazaki, Takayuki Shiratsuchi, Naohiro Terada, Derek J Hook, Michael A Walters, Gunda I Georg, Jon E Hawkinson

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

Article in Journal of biomolecular screening, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.5field-weighted citation impact, top 29% 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

9 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Biomolecules · 2022
    Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. 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 4 institutions in 2 countries.

Yujian ZhangOtsuka Maryland Medicinal Laboratories, Inc., Rockville, MD, USA.
Defeng TianInstitute for Therapeutics Discovery & Development, University of Minnesota, Minneapolis, MN, USA.
Hironori MatsuyamaOtsuka Maryland Medicinal Laboratories, Inc., Rockville, MD, USA.
Takashi HamazakiDepartment of Pediatrics, Osaka City University Graduate School of Medicine, Abeno-ku, Osaka, Japan.
Takayuki ShiratsuchiOtsuka Maryland Medicinal Laboratories, Inc., Rockville, MD, USA.
Naohiro TeradaDepartment of Pathology, University of Florida College of Medicine, Gainesville, FL, USA.
Derek J HookInstitute for Therapeutics Discovery & Development, University of Minnesota, Minneapolis, MN, USA.
Michael A WaltersInstitute for Therapeutics Discovery & Development, University of Minnesota, Minneapolis, MN, USA.
Gunda I GeorgInstitute for Therapeutics Discovery & Development, University of Minnesota, Minneapolis, MN, USA.
Jon E HawkinsonInstitute for Therapeutics Discovery & Development, University of Minnesota, Minneapolis, MN, USA hawkinso@umn.edu.
University of Minnesota · USOtsuka (United States) · USFlorida College · USOsaka City University · JP

Funding

Drug Discovery & Synthesis of Contraceptive AgentsU01HD076542 · NICHD · UNIVERSITY OF MINNESOTA · PI GEORG, GUNDA I. · 2012 to 2016
$5.0M
Developing Male Contraceptives by Targeting ANT4U01HD060474 · NICHD · UNIVERSITY OF FLORIDA · PI TERADA, NAOHIRO · 2009 to 2013
$1.2M
NICHD NIH HHS HHSN275201300017CNICHD NIH HHS HHSN275201300017INICHD NIH HHS U01 HD060474NICHD NIH HHS U01 HD076542PHS HHS HHSN275201300017C
6 · The paper itself

Abstract

Transport of ADP and ATP across mitochondria is one of the primary points of regulation to maintain cellular energy homeostasis. This process is mainly mediated by adenine nucleotide translocase (ANT) located on the mitochondrial inner membrane. There are four human ANT isoforms, each having a unique tissue-specific expression pattern and biological function, highlighting their potential as drug targets for diverse clinical indications, including male contraception and cancer. In this study, we present a novel yeast-based high-throughput screening (HTS) strategy to identify compounds inhibiting the function of ANT. Yeast strains generated by deletion of endogenous proteins with ANT activity followed by insertion of individual human ANT isoforms are sensitive to cell-permeable ANT inhibitors, which reduce proliferation. Screening hits identified in the yeast proliferation assay were characterized in ADP/ATP exchange assays employing recombinant ANT isoforms expressed in isolated yeast mitochondria and Lactococcus lactis as well as by oxygen consumption rate in mammalian cells. Using this approach, closantel and CD437 were identified as broad-spectrum ANT inhibitors, whereas leelamine was found to be a modulator of ANT function. This yeast "knock-out/knock-in" screening strategy is applicable to a broad range of essential molecular targets that are required for yeast survival.

Indexed as

High-Throughput Screening AssaysAbietanesAdenosine TriphosphateBiological TransportCell ProliferationHumansLactococcus lactisMitochondriaMitochondrial ADP, ATP TranslocasesOrganisms, Genetically ModifiedRetinoidsSaccharomyces cerevisiaeSalicylanilidesSmall Molecule LibrariesTransgenesAbietanesAdenosine TriphosphateCD 437closanteldehydroabietylamineMitochondrial ADP, ATP TranslocasesRetinoidsSalicylanilidesSmall Molecule Librariesadenine nucleotide translocaseADP/ATP exchangehigh throughput screeningLactococcus lactisyeast mitochondria

Identifiers

PMID26746582
PMCPMC6559718
OpenAlexW2331150521

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.