Evidence map›Paper›PMID 40767969›Full record

ArticleJournal of the American Chemical Society2025

Deubiquitinase-Targeting Chimeras Mediated Stabilization of Tumor Suppressive E3 Ligase Proteins as a Strategy for Cancer Therapy.

Li Chen, Zhijie Deng, Yan Xiong, Jing Liu, Daoyuan Huang, Jingchao Wang, Yong Chen, Hiroyuki Inuzuka, Ling Xie, Xian Chen and 2 more

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
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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

12 authors.

Li ChenDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.
Zhijie DengMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Yan XiongMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Jing LiuDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.
Daoyuan HuangDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.
Jingchao WangDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.
Yong ChenDivision of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.
Hiroyuki InuzukaDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.
Ling XieDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Xian ChenDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Jian JinMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Sciences, Oncological Sciences and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.ORCID 0000-0002-2387-3862
Wenyi WeiDepartment of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, United States.ORCID 0000-0003-0512-3811

Funding

Deciphering the physiological role and interplay between ubiquitination and phosphorylation pathways to guide targeted cancer therapiesR35CA253027 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Wenyi Wei · 2020 to 2026
$6.2M
An AVANCE NEO 400 MHz NMR Spectrometer for Chemical Biology and Drug DiscoveryS10OD028504 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ZHOU, MING-MING · 2020 to 2020
$599k
An AVANCE NEO 600 MHz NMR Spectrometer System for Structural and Chemical BiologyS10OD025132 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ZHOU, MING-MING · 2019 to 2019
$535k
NCI NIH HHS R35 CA253027NIH HHS S10 OD025132NIH HHS S10 OD028504
6 · The paper itself

Abstract

Targeted protein stabilization has emerged as a promising therapeutic strategy to combat various human diseases linked to aberrant protein degradation. However, the deubiquitinase-targeting chimera (DUBTAC) technology is still in its infancy, with only a few proteins being successfully stabilized. To this end, the stabilization of tumor suppressor proteins represents a critical therapeutic strategy to combat cancer, as their loss-of-function mutations and reduced expression are frequently implicated in the pathogenesis of diverse types of human cancer. In this study, we present an innovative PRO-DUBTAC platform that, for the first time, stabilizes tumor-suppressive E3 ubiquitin ligases as a novel anticancer therapeutic approach. Through the conjugation of E3 ligase ligands with a small-molecule ligand of the deubiquitinase OTUB1

Indexed as

Antineoplastic AgentsDeubiquitinating EnzymesKelch-Like ECH-Associated Protein 1NeoplasmsUbiquitin-Protein LigasesVon Hippel-Lindau Tumor Suppressor ProteinCell Line, TumorHumansProtein StabilityAntineoplastic AgentsDeubiquitinating EnzymesKEAP1 protein, humanKelch-Like ECH-Associated Protein 1OTUB1 protein, humanUbiquitin-Protein LigasesVHL protein, humanVon Hippel-Lindau Tumor Suppressor Protein

Identifiers

PMID40767969
PMCPMC12395470

What OpenQuestion holds

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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.