Evidence map›Paper›PMID 39905966›Full record

ArticleJournal of medicinal chemistry2025

Structure-Activity Relationship Studies of DNA Methyltransferase 1 Monovalent Degraders.

Chao Qian, Youngeun Lee, Yulin Han, Yue Zhong, Jujun Zhou, Joel Hrit, Ling Xie, Qin Chen, H Ümit Kaniskan, Xian Chen and 4 more

Abstract read
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 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

14 authors.

Chao QianMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Science, Oncological Science and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Youngeun LeeMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Science, Oncological Science and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.ORCID 0000-0002-0081-3269
Yulin HanMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Science, Oncological Science and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Yue ZhongMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Science, Oncological Science and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Jujun ZhouDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.ORCID 0000-0003-4104-7158
Joel HritDepartment of Epigenetics, Van Andel Institute, Grand Rapids, Michigan 49503, United States.
Ling XieDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Qin ChenDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
H Ümit KaniskanMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Science, Oncological Science and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Xian ChenDepartment of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Scott RothbartDepartment of Epigenetics, Van Andel Institute, Grand Rapids, Michigan 49503, United States.
Xiaodong ChengDepartment of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, United States.
Yan XiongMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Science, Oncological Science and Neuroscience, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, United States.
Jian JinMount Sinai Center for Therapeutics Discovery, Departments of Pharmacological Science, Oncological Science and Neuroscience, Tisch Cancer Institute, 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
Epigenetic regulations of DNA and histone methylation and deMethylation: Structures and MechanismsR35GM134744 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Xiaodong Cheng · 2020 to 2026
$4.5M
Mechanisms of DNA methylation signaling and dysregulation in colon cancerR01CA283463 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI Scott Rothbart · 2024 to 2026
$3.2M
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
Preclinical studies of non-nucleoside DNMT3A/3B inhibitorsR21CA277152 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI CHEN, TAIPING, CHENG, XIAODONG · 2024 to 2025
$417k
Defining the regulation of UHRF1 and DNMT1 for maintenance of the epigenomeF32CA260116 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI HRIT, JOEL · 2021 to 2023
$208k
NCI NIH HHS F32 CA260116NCI NIH HHS R01 CA283463NCI NIH HHS R21 CA277152NCI NIH HHS T32 CA078207NIGMS NIH HHS R35 GM134744NIH HHS S10 OD025132NIH HHS S10 OD028504
6 · The paper itself

Abstract

DNA methyltransferase 1 (DNMT1), which catalyzes maintenance methylation of hemimethylated DNA during DNA replication, is overexpressed in cancer. Recently, the first-in-class DNMT1-selective noncovalent small-molecule inhibitors, GSK3484862 and GSK3685032, were discovered. These inhibitors were also reported to degrade DNMT1. However, structure-activity relationship (SAR) studies of these monovalent DNMT1 degraders are lacking. Here, we report our SAR studies of this scaffold on degrading DNMT1, which led to the discovery of multiple lead degraders, including compound

Indexed as

DNA (Cytosine-5-)-Methyltransferase 1Antineoplastic AgentsCell Line, TumorEnzyme InhibitorsHumansProteolysisStructure-Activity RelationshipUbiquitin-Protein LigasesAntineoplastic AgentsDNA (Cytosine-5-)-Methyltransferase 1DNMT1 protein, humanEnzyme InhibitorsUbiquitin-Protein Ligases

Identifiers

PMID39905966
PMCPMC11932022

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.