Evidence map›Paper›PMID 24290880›Full record

ArticleChemistry & biology2013

A small-molecule inducer of PDX1 expression identified by high-throughput screening.

Yuan Yuan, Kate Hartland, Zarko Boskovic, Yikai Wang, Deepika Walpita, Philippe A Lysy, Cheng Zhong, Damian W Young, Young-Kwon Kim, Nicola J Tolliday and 3 more

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

Article in Chemistry & biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

15 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Small-molecule discovery in the pancreatic beta cell.Current opinion in chemical biology · 2022
    Review
  5. Review
  6. Review
  7. Epigenetic Control of Endocrine Pancreas DifferentiationFrontiers in cell and developmental biology · 2018
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Targeting the pancreatic β-cell to treat diabetes.Nature reviews. Drug discovery · 2014
    Review
  14. Article
  15. Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

13 authors at 2 institutions in 2 countries.

Yuan YuanChemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Kate HartlandChemical Biology Platform, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Zarko BoskovicChemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Yikai WangChemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Deepika WalpitaChemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Philippe A LysyLaboratory of Pediatric Hepatology and Cell Therapy, Catholic University of Leuven, Brussels 1200, Belgium.
Cheng ZhongChemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Damian W YoungChemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Young-Kwon KimChemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Nicola J TollidayChemical Biology Platform, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Etienne M SokalLaboratory of Pediatric Hepatology and Cell Therapy, Catholic University of Leuven, Brussels 1200, Belgium.
Stuart L SchreiberChemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Bridget K WagnerChemical Biology Program, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: bwagner@broadinstitute.org.
Broad Institute · USKU Leuven · BE

Funding

SYNTHESIS OF MATERIALS WITH PHYSIOLOGICAL PROPERTIESR01GM038627 · NIGMS · YALE UNIVERSITY · PI SCHREIBER, STUART L · 1987 to 2017
$10.5M
Small-molecule approaches to restore glycemic control in type 1 diabetesDP2DK083048 · NIDDK · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI WAGNER, BRIDGET K · 2008 to 2010
$2.6M
SYNTHESIS OF MATERIALS WITH PHYSIOLOGICAL PROPERTIESR37GM038627 · NIGMS · HARVARD UNIVERSITY · PI SCHREIBER, STUART L · 1992 to 2001
$1.1M
Howard Hughes Medical InstituteNIDDK NIH HHS DP2 DK083048NIGMS NIH HHS GM38627NIGMS NIH HHS R01 GM038627NIGMS NIH HHS R37 GM038627
6 · The paper itself

Abstract

Pancreatic and duodenal homeobox 1 (PDX1), a member of the homeodomain-containing transcription factor family, is a key transcription factor important for both pancreas development and mature β cell function. The ectopic overexpression of Pdx1, Neurog3, and MafA in mice reprograms acinar cells to insulin-producing cells. We developed a quantitative PCR-based gene expression assay to screen more than 60,000 compounds for expression of each of these genes in the human PANC-1 ductal carcinoma cell line. We identified BRD7552, which upregulated PDX1 expression in both primary human islets and ductal cells, and induced epigenetic changes in the PDX1 promoter consistent with transcriptional activation. Prolonged compound treatment induced both insulin mRNA and protein and also enhanced insulin expression induced by the three-gene combination. These results provide a proof of principle for identifying small molecules that induce expression of transcription factors to control cellular reprogramming.

Indexed as

AnimalsCarcinoma, DuctalCarcinoma, Pancreatic DuctalCell Line, TumorGene Expression Regulation, NeoplasticHigh-Throughput Screening AssaysHomeodomain ProteinsHumansMicePolymerase Chain ReactionPromoter Regions, GeneticSmall Molecule LibrariesTrans-ActivatorsTranscriptional ActivationHomeodomain Proteinspancreatic and duodenal homeobox 1 proteinSmall Molecule LibrariesTrans-Activators

Identifiers

PMID24290880
PMCPMC3927138
OpenAlexW2090830096

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.