Evidence map›Paper›PMID 35749470›Full record

ArticleACS chemical biology2022

Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC.

Jake C Swartzel, Michael J Bond, Andreas P Pintado-Urbanc, Mehana Daftary, Mackenzie W Krone, Todd Douglas, Evan J Carder, Joshua T Zimmer, Takahiro Maeda, Matthew D Simon and 1 more

Open access · greenAbstract read
In one paragraph

Article in ACS chemical biology, 2022. 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
1.0field-weighted citation impact, top 25% 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. International journal of molecular sciences · 2026
    Article
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  7. Uridine as a hub in cancer metabolism and RNA biology.Experimental & molecular medicine · 2025
    Review
  8. Article
  9. Aberrant pre-mRNA processing in cancer.The Journal of experimental medicine · 2024
    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 at 3 institutions in 2 countries.

Jake C SwartzelDepartment of Chemistry, Yale University, New Haven, Connecticut 06511, United States.
Michael J BondDepartment of Pharmacology, Yale University, New Haven, Connecticut 06511, United States.
Andreas P Pintado-UrbancDepartment of Chemistry, Yale University, New Haven, Connecticut 06511, United States.
Mehana DaftaryDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06511, United States.
Mackenzie W KroneDepartment of Molecular, Cellular, and Developmental Biology, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06511, United States.
Todd DouglasDepartment of Molecular, Cellular, and Developmental Biology, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06511, United States.
Evan J CarderDepartment of Molecular, Cellular, and Developmental Biology, Yale University, 260 Whitney Avenue, New Haven, Connecticut 06511, United States.ORCID 0000-0001-5727-0632
Joshua T ZimmerInstitute for Biomolecular Design and Discovery, Yale University, West Haven, Connecticut 06516, United States.
Takahiro MaedaDivision of Precision Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka 812-8582, Japan.
Matthew D SimonInstitute for Biomolecular Design and Discovery, Yale University, West Haven, Connecticut 06516, United States.ORCID 0000-0001-7423-5265
Craig M CrewsDepartment of Chemistry, Yale University, New Haven, Connecticut 06511, United States.ORCID 0000-0002-8456-2005
Yale University · USWhitney Museum of American Art · USKyushu University · JP

Funding

Inducing Proximity: An Emerging Paradigm for New Therapeutic ModalitiesR35CA197589 · NCI · YALE UNIVERSITY · PI CRAIG M CREWS · 2015 to 2026
$10.7M
Predoc Training at the Interface Chemistry and BiologyT32GM067543 · NIGMS · YALE UNIVERSITY · PI CRAWFORD, JASON MICHAEL · 2003 to 2022
$7.4M
Development of a Tumor-Specific PROTACF31CA232477 · NCI · YALE UNIVERSITY · PI BOND, MICHAEL JOSEPH · 2018 to 2020
$120k
NCI NIH HHS F31 CA232477NCI NIH HHS R35 CA197589NIGMS NIH HHS T32 GM067543
6 · The paper itself

Abstract

The RNA decapping scavenger protein, DcpS, has recently been identified as a dependency in acute myeloid leukemia (AML). The potent DcpS inhibitor RG3039 attenuates AML cell viability, and shRNA knockdown of DcpS is also antiproliferative. Importantly, DcpS was found to be non-essential in normal human hematopoietic cells, which opens a therapeutic window for AML treatment by DcpS modulation. Considering this strong DcpS dependence in AML cell lines, we explored PROTAC-mediated degradation as an alternative strategy to modulate DcpS activity. Herein, we report the development of JCS-1, a PROTAC exhibiting effective degradation of DcpS at nanomolar concentrations. JCS-1 non-covalently binds DcpS with a RG3039-based warhead and recruits the E3 ligase VHL, which induces potent, rapid, and sustained DcpS degradation in several AML cell lines. JCS-1 serves as a chemical biology tool to interrogate DcpS degradation and associated changes in RNA processes in different cellular contexts, which may be an attractive strategy for the treatment of AML and other DcpS-dependent genetic disorders.

Indexed as

EndoribonucleasesLeukemia, Myeloid, AcuteHumansRNA, Small InterferingVon Hippel-Lindau Tumor Suppressor ProteinDcpS protein, humanEndoribonucleasesmRNA decapping enzymesRNA, Small InterferingVHL protein, humanVon Hippel-Lindau Tumor Suppressor Protein

Identifiers

PMID35749470
PMCPMC10367122
OpenAlexW4283388590

What OpenQuestion holds

Textmetadata
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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.