Evidence map›Paper›PMID 26195741›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Small-molecule enhancers of autophagy modulate cellular disease phenotypes suggested by human genetics.

Szu-Yu Kuo, Adam B Castoreno, Leslie N Aldrich, Kara G Lassen, Gautam Goel, Vlado Dančík, Petric Kuballa, Isabel Latorre, Kara L Conway, Sovan Sarkar and 6 more

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

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
5.2field-weighted citation impact, top 4% 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

46 citing papers in PubMed, 68 citations in OpenAlex.

  1. Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026
    Review
  2. Article
  3. Restricting intracellularAutophagy · 2026
    Article
  4. Review
  5. Article
  6. Autophagy-NADFrontiers in molecular biosciences · 2025
    Review
  7. Review
  8. Hapalindole Q suppresses autophagosome-lysosome fusion by promoting YAP1 degradation via chaperon-mediated autophagy.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  9. BCL2 regulates antibacterial autophagy in the intestinal epithelium.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  10. Autophagy3D: a comprehensive autophagy structure database.Database : the journal of biological databases and curation · 2024
    Article
  11. Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024
    Review
  12. Article
  13. Review
  14. Article
  15. On the linkage of thermodynamics and pathogenicity.Current opinion in structural biology · 2023
    Review
  16. Article
  17. Review
  18. Small molecule probes for targeting autophagy.Nature chemical biology · 2021
    Review
  19. Article
  20. 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

16 authors at 5 institutions in 3 countries.

Szu-Yu KuoCenter for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142; Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138;
Adam B CastorenoCenter for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142;
Leslie N AldrichCenter for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138;
Kara G LassenCenter for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142;
Gautam GoelCenter for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114;
Vlado DančíkCenter for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142;
Petric KuballaCenter for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114;
Isabel LatorreCenter for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142;
Kara L ConwayCenter for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142;
Sovan SarkarWhitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142; Institute of Biomedical Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, United Kingdom;
Dorothea MaetzelWhitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142;
Rudolf JaenischWhitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA 02142; Skolkovo Institute of Science and Technology (Skoltech), Skolkovo 143025, Moscow Region, Russia;
Paul A ClemonsCenter for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142;
Stuart L SchreiberCenter for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138; Howard Hughes Medical Institute, Cambridge, MA 02142 stuart_schreiber@harvard.edu ashamji@broadinstitute.org xavier@molbio.mgh.harvard.edu.
Alykhan F ShamjiCenter for the Science of Therapeutics, Broad Institute, Cambridge, MA 02142; stuart_schreiber@harvard.edu ashamji@broadinstitute.org xavier@molbio.mgh.harvard.edu.
Ramnik J XavierCenter for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114; Program in Medical and Population Genetics, Broad Institute, Cambridge, MA 02142; Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, MA 02114; stuart_schreiber@harvard.edu ashamji@broadinstitute.org xavier@molbio.mgh.harvard.edu.
Broad Institute · USMassachusetts General Hospital · USWhitehead Institute for Biomedical Research · USHoward Hughes Medical Institute · USMassachusetts Institute of Technology · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Genetic and Pathway Analysis CoreU19AI109725 · NIAID · WASHINGTON UNIVERSITY · PI VIRGIN, HERBERT W · 2014 to 2018
$32.7M
Transcriptional condensates, epigenetic editing and Rett SyndromeR01MH104610 · NIMH · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF, YOUNG, RICHARD · 2014 to 2023
$7.4M
An iPSC based platform for functionally assessing genetic and environmental riskR01NS088538 · NINDS · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI JAENISCH, RUDOLF, MYERS, RICHARD H · 2014 to 2018
$5.0M
Cancer dependencies associated with genomic alterations and targeted by small molU01CA176152 · NCI · BROAD INSTITUTE, INC. · PI SCHREIBER, STUART L · 2013 to 2016
$4.4M
ATG16L1 T300A: genetics to biologyR01DK097485 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI XAVIER, RAMNIK J · 2013 to 2021
$4.1M
Howard Hughes Medical InstituteNCI NIH HHS U01 CA176152NCI NIH HHS U01CA176152NIAID NIH HHS U19 AI109725NIAID NIH HHS U19AI109725NIDDK NIH HHS DK097485NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK097485NIMH NIH HHS MH104610NIMH NIH HHS R01 MH104610NINDS NIH HHS R01 NS088538NINDS NIH HHS R01-NS088538
6 · The paper itself

Abstract

Studies of human genetics and pathophysiology have implicated the regulation of autophagy in inflammation, neurodegeneration, infection, and autoimmunity. These findings have motivated the use of small-molecule probes to study how modulation of autophagy affects disease-associated phenotypes. Here, we describe the discovery of the small-molecule probe BRD5631 that is derived from diversity-oriented synthesis and enhances autophagy through an mTOR-independent pathway. We demonstrate that BRD5631 affects several cellular disease phenotypes previously linked to autophagy, including protein aggregation, cell survival, bacterial replication, and inflammatory cytokine production. BRD5631 can serve as a valuable tool for studying the role of autophagy in the context of cellular homeostasis and disease.

Indexed as

Genetics, MedicalAutophagyBacteriaCarrier ProteinsCell AggregationGreen Fluorescent ProteinsHeLa CellsHigh-Throughput Screening AssaysHumansInduced Pluripotent Stem CellsInterleukin-1betaIntracellular Signaling Peptides and ProteinsMembrane GlycoproteinsModels, BiologicalNeuronsNiemann-Pick C1 ProteinCarrier Proteinsenhanced green fluorescent proteinGreen Fluorescent ProteinsInterleukin-1betaIntracellular Signaling Peptides and ProteinsMembrane GlycoproteinsNiemann-Pick C1 ProteinNPC1 protein, humanPeptidespolyglutamineSmall Molecule LibrariesautophagyCrohn’s diseasehigh-throughput screeningsmall-molecule probes

Identifiers

PMID26195741
PMCPMC4534235
OpenAlexW2096649028

What OpenQuestion holds

Textmetadata
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.