Evidence map›Paper›PMID 41526361›Full record

ArticleNature communications2026

Small molecule splicing modulators that disrupt O-GlcNAc homeostasis.

Steven S Cheng, Alison C Mody, Amedeo Vetere, Ashwin Govindan, Yewon Lee, Danielle E Khost, Rohan Narayan, Timothy B Sackton, Nicholas K Conrad, Bridget K Wagner and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. 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
–field-weighted citation impact
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.

  1. Review
  2. Review
  3. Article
  4. Review
  5. 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

11 authors.

Steven S ChengDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Alison C ModyDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Amedeo VetereChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Ashwin GovindanDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0003-1759-707X
Yewon LeeDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Danielle E KhostInformatics Group, Harvard University, Cambridge, MA, USA.
Rohan NarayanDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8783-7636
Timothy B SacktonInformatics Group, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1673-9216
Nicholas K ConradDepartment of Microbiology, UT Southwestern Medical Center, Dallas, TX, USA.
Bridget K WagnerChemical Biology and Therapeutics Science Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Christina M WooDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA. cwoo@chemistry.harvard.edu.ORCID http://orcid.org/0000-0001-8687-9105

Funding

Mechanisms regulating KSHV transcription elongation and terminationR01AI153175 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI CONRAD, NICHOLAS K · 2021 to 2025
$2.3M
Writing and erasing O-GlcNAc on target proteins in the brainRF1AG081475 · NIA · HARVARD UNIVERSITY · PI WOO, CHRISTINA · 2023 to 2023
$1.8M
New tools for studying GlcNAc biologyU01CA242115 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI KOHLER, JENNIFER J · 2019 to 2021
$1.5M
NCI NIH HHS U01 CA242115NIAID NIH HHS R01 AI153175NIA NIH HHS RF1 AG081475U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER) 1RF1AG081475U.S. Department of Health & Human Services | NIH | Office of Extramural Research, National Institutes of Health (OER) AI153175, CA242115
6 · The paper itself

Abstract

O-Linked N-acetylglucosamine (O-GlcNAc) is a nucleocytoplasmic post-translational modification that is tightly regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Dysregulation of O-GlcNAc in human disease has motivated efforts to therapeutically modulate O-GlcNAc. Drug repurposing efforts can accelerate these campaigns and unveil how clinically relevant compounds and pathways intersect with O-GlcNAc. Here we report the results of three parallel drug repurposing screens against the O-GlcNAc cycling enzymes in cells and in vitro that reveal kinase inhibitors GSK690693 and Y-33075 act as splicing modulators that disrupt O-GlcNAc homeostasis and simultaneously downregulate OGT and OGA. These effects are independent of their respective annotated targets, AKT and ROCK, and are distinct from OGT and OGA inhibitors and similar kinase inhibitors. Evaluation of a panel of splicing modulators revealed three additional potent compounds (OTS964, indisulam, GNF2133) that similarly downregulate OGT and OGA with distinct splicing profiles. These findings reveal previously unobserved splicing modulator chemotypes and approaches to disrupt O-GlcNAc homeostasis.

Indexed as

AcetylglucosamineHomeostasisRNA Splicingbeta-N-AcetylhexosaminidasesDown-RegulationGlycosylationHEK293 CellsHumansN-AcetylglucosaminyltransferasesProtein Kinase InhibitorsProtein Processing, Post-TranslationalThiazolesAcetylglucosaminebeta-N-Acetylhexosaminidaseshexosaminidase CN-AcetylglucosaminyltransferasesO-GlcNAc transferaseOGT protein, humanProtein Kinase InhibitorsThiazoles

Identifiers

PMID41526361
PMCPMC12894984

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.