Evidence map›Paper›PMID 40232306›Full record

ArticleJournal of medicinal chemistry2025

Discovery of a Potent and Selective Protein Arginine Methyltransferase 5 (PRMT5) PROTAC Degrader.

Yue Zhong, Huensuk Kim, Chao Qian, Ling Xie, Xian Chen, Yan Xiong, Jacqueline Hu, Matthew Chen, Ernesto Guccione, Yudao Shen and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of medicinal chemistry, 2025. 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. PROTACs in cancer therapy: targeted degradation of GPX4, PARP and epigenetic regulators.Journal of enzyme inhibition and medicinal chemistry · 2026
    Review
  2. Review
  3. Discovery of a Highly Potent and Selective ENL Degrader.Journal of medicinal chemistry · 2026
    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.

Yue ZhongMount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Huensuk KimMount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Chao QianMount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York 10029, 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.
Yan XiongMount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Jacqueline HuMount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Matthew ChenMount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Ernesto GuccioneDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Yudao ShenMount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.ORCID 0009-0006-6031-4302
Jian JinMount Sinai Center for Therapeutics Discovery, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.ORCID 0000-0002-2387-3862

Funding

TRAINING PROGRAM IN CANCER THERAPYT32CA078207 · NCI · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI James J Manfredi · 1999 to 2026
$11.6M
Teaching biomedical and pharmacological trainees to produce FAIR data for AI & ML applicationsT32GM062754 · NIGMS · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SCHLESSINGER, AVNER · 2001 to 2023
$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 T32 CA078207NIGMS NIH HHS T32 GM062754NIH HHS S10 OD025132NIH HHS S10 OD028504
6 · The paper itself

Abstract

Protein arginine methyltransferase 5 (PRMT5) plays crucial roles in the regulation of various biological processes through the mono- and symmetric dimethylation of protein substrates. PRMT5 is overexpressed in various human cancers and its overexpression is associated with poor prognosis. We previously reported the first-in-class PRMT5 degrader, MS4322, which is also the only von Hippel-Lindau (VHL)-recruiting PRMT5 degrader to date. Here, we performed structure-activity relationship (SAR) studies exploring various linkers and ligands of VHL and PRMT5, which resulted in the best-in-class PRMT5 degrader, MS115 (compound

Indexed as

Antineoplastic AgentsDrug DiscoveryProtein-Arginine N-MethyltransferasesAdaptor Proteins, Signal TransducingCell Line, TumorCell ProliferationHumansProteolysisStructure-Activity RelationshipTranscription FactorsVon Hippel-Lindau Tumor Suppressor ProteinAdaptor Proteins, Signal TransducingAntineoplastic AgentsPRMT5 protein, humanProtein-Arginine N-MethyltransferasesTranscription FactorsVHL protein, humanVon Hippel-Lindau Tumor Suppressor ProteinWDR77 protein, human

Identifiers

PMID40232306
PMCPMC12080994

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.