Evidence map›Paper›PMID 41254147›Full record

ArticleCommunications chemistry2025

A Hybrid compound H93 treats prostate cancer by directly binding UHRF1 and promoting protein dimerization.

Yuxin Fu, Longying Jiang, Guojian Xie, Yuchong Peng, Yongming Fu, Qianling Zhu, Youhong Liu, Guilong Zhao, Xueke Liu, Yongbo Peng and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Yuxin Fu *Xiangya Cancer Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.ORCID http://orcid.org/0000-0001-8626-9040
Longying Jiang *Department of Pathology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.ORCID http://orcid.org/0000-0002-3920-9878
Guojian XieChangsha Hoozi Biological Science and Technology Co. Ltd, Changsha, China.
Yuchong PengKey Laboratory of Clinical Precision Pharmacy of Guangdong Higher Education Institutes, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, China.
Yongming FuKey Laboratory of Clinical Precision Pharmacy of Guangdong Higher Education Institutes, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, China.
Qianling ZhuXiangya Cancer Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Youhong LiuXiangya Cancer Center, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Guilong ZhaoZhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, China.
Xueke LiuDepartment of Pathology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Yongbo PengCollege of Pharmacy, Chongqing Medical University, Chongqing, China.
Yongheng ChenDepartment of Pathology, NHC Key Laboratory of Cancer Proteomics, State Local Joint Engineering Laboratory for Anticancer Drugs, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. yonghenc@163.com.ORCID http://orcid.org/0000-0001-8139-6892
Xiong LiKey Laboratory of Clinical Precision Pharmacy of Guangdong Higher Education Institutes, The First Affiliated Hospital, Guangdong Pharmaceutical University, Guangzhou, China. lixiong@gdpu.edu.cn.ORCID http://orcid.org/0000-0003-3547-4401

Funding

Hunan Provincial Science and Technology Department (Department of Science and Technology of Hunan Province) 2021RC4012National Natural Science Foundation of China (National Science Foundation of China) 81572542National Natural Science Foundation of China (National Science Foundation of China) 81974074National Natural Science Foundation of China (National Science Foundation of China) 82172654
6 · The paper itself

Abstract

UHRF1 is a pivotal epigenetic regulator bridging DNA methylation and histone modifications, frequently overexpressed in prostate cancer (PCa). However, no UHRF1-targeted therapeutics have advanced to clinical trials. Here, we report the development of H93, a hybrid small molecule integrating functional groups derived from NSC232003 and vorinostat, respectively. H93 exhibits potent anticancer activity in vitro, correlating with UHRF1 protein abundance, and co-crystallization studies confirm that H93 directly binding to the SRA domain of UHRF1. Intriguingly, H93 promotes UHRF1 dimerization, generating a defined binding pocket that stabilizes compound engagement and enhances druggability of UHRF1 as a non-kinase target. Dimerized UHRF1 adopts a "closed" conformation that disrupts its interaction with DNMT1, impairs DNA methylation maintenance, and reactivates epigenetically silenced tumor suppressor genes. In vivo, H93 demonstrates significant antitumor efficacy. Overall, this study elucidates the structural and mechanistic basis of H93, establishing it as a promising UHRF1-targeted therapy for PCa.

Identifiers

PMID41254147
PMCPMC12627547

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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.