Evidence map›Paper›PMID 34129829›Full record

ArticleCell chemical biology2021

Identification and validation of selective deubiquitinase inhibitors.

Anthony C Varca, Dominick Casalena, Wai Cheung Chan, Bin Hu, Robert S Magin, Rebekka M Roberts, Xiaoxi Liu, He Zhu, Hyuk-Soo Seo, Sirano Dhe-Paganon and 3 more

Open access · greenAbstract read
In one paragraph

Article in Cell chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

19 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
  2. Article
  3. Small-molecule allosteric activator of ubiquitin-specific protease 7 (USP7).Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Role of Ubiquitin-regulated EMT in Cancer Metastasis and Chemoresistance.International journal of biological sciences · 2025
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. 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

13 authors at 1 institution in 1 country.

Anthony C VarcaDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Dominick CasalenaFAST Lab, Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Wai Cheung ChanDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Bin HuDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Robert S MaginDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Rebekka M RobertsDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Xiaoxi LiuDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
He ZhuDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Hyuk-Soo SeoDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Sirano Dhe-PaganonDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jarrod A MartoDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Douglas AuldFAST Lab, Chemical Biology and Therapeutics, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Sara J BuhrlageDepartment of Cancer Biology and the Linde Program in Cancer Chemical Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA. Electronic address: saraj_buhrlage@dfci.harvard.edu.
Dana-Farber Cancer Institute · US

Funding

Novel Screening Platform for Discovery of DUB Targeting ProbesR01CA233800 · NCI · DANA-FARBER CANCER INST · PI BUHRLAGE, SARA J, MARTO, JARROD A. · 2019 to 2022
$2.5M
Tools for DUB Drug DiscoveryR21CA247671 · NCI · DANA-FARBER CANCER INST · PI BUHRLAGE, SARA J, MARTO, JARROD A. · 2020 to 2021
$648k
NCI NIH HHS R01 CA233800NCI NIH HHS R21 CA247671
6 · The paper itself

Abstract

Deubiquitinating enzymes (DUBs) are a class of isopeptidases that regulate ubiquitin dynamics through catalytic cleavage of ubiquitin from protein substrates and ubiquitin precursors. Despite growing interest in DUB biological function and potential as therapeutic targets, few selective small-molecule inhibitors and no approved drugs currently exist. To identify chemical scaffolds targeting specific DUBs and establish a broader framework for future inhibitor development across the gene family, we performed high-throughput screening of a chemically diverse small-molecule library against eight different DUBs, spanning three well-characterized DUB families. Promising hit compounds were validated in a series of counter-screens and orthogonal assays, as well as further assessed for selectivity across expanded panels of DUBs. Through these efforts, we have identified multiple highly selective DUB inhibitors and developed a roadmap for rapidly identifying and validating selective inhibitors of related enzymes.

Indexed as

Deubiquitinating EnzymesEnzyme InhibitorsFemaleHEK293 CellsHumansMolecular StructureSmall Molecule LibrariesDeubiquitinating EnzymesEnzyme InhibitorsSmall Molecule Librariesdeubiquitinasehigh-throughput screeningsmall-molecule inhibitor

Identifiers

PMID34129829
PMCPMC9473745
OpenAlexW3168940517

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.