Evidence map›Paper›PMID 42710907›Full record

ArticleJournal of enzyme inhibition and medicinal chemistry2026

Cryo-EM structure-based discovery of etravirine as a specific inhibitor of PRMT5/pICln protein-protein interaction for prostate cancer treatment.

Zhixia Chi, Xueyong Xu, Zhihang Shen, Xuehong Deng, Bennett D Elzey, Chenglong Li, Wen Jiang, Chang-Deng Hu

Abstract read
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In one paragraph

Article in Journal of enzyme inhibition and medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Zhixia ChiDepartment of Chemistry, Purdue University, West Lafayette, Indiana, USA.
Xueyong XuDepartment of Biological Sciences, Purdue University, West Lafayette, Indiana, USA.
Zhihang ShenDepartment of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Xuehong DengDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.
Bennett D ElzeyDepartment of Comparative Pathobiology, Purdue University, West Lafayette, Indiana, USA.
Chenglong LiDepartment of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville, FL, USA.
Wen JiangDepartment of Biological Sciences, Purdue University, West Lafayette, Indiana, USA.
Chang-Deng HuDepartment of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.

Funding

Role and targeting of PRMT5 in prostate cancerR01CA212403 · NCI · PURDUE UNIVERSITY · PI HUANG, JIAOTI, LI, CHENGLONG · 2017 to 2021
$3.0M
NCI NIH HHS R01 CA212403
6 · The paper itself

Abstract

Protein arginine methyltransferase 5 (PRMT5) is overexpressed in many cancers and correlates with poor patient survival. In prostate cancer, PRMT5 cooperates with its cofactor pICln to promote tumour growth by epigenetically activating androgen receptor (AR) expression. Using a near-atomic cryo-EM structure of PRMT5/MEP50/pICln complex, we identified a previously undefined, pICln-specific protein-protein interaction (PPI) interface on PRMT5, termed P4I. Structure-based virtual screening identified the FDA-approved compound etravirine as a binder to this site. BiFC, Co-IP, and PLA assays confirmed that etravirine disrupts PRMT5/pICln interaction. A cryo-EM structure of PRMT5/MEP50/etravirine further validated on-target binding at P4I. Functionally, etravirine reduced prostate cancer cell proliferation, inhibited tumour growth, and downregulated AR and AR-V7 expression in cells and in mouse models. These results demonstrate that the unique P4I interface is a promising therapeutic target and that etravirine serves as a proof-of-concept lead compound for exploring the potential of P4I-targeted strategies in prostate cancer.

Indexed as

Antineoplastic AgentsDrug DiscoveryEnzyme InhibitorsProstatic NeoplasmsProtein-Arginine N-MethyltransferasesPyridazinesAnimalsCell ProliferationDose-Response Relationship, DrugDrug Screening Assays, AntitumorHumansMaleMiceModels, MolecularMolecular StructureNitrilesAntineoplastic AgentsEnzyme InhibitorsetravirineNitrilesPRMT5 protein, humanProtein-Arginine N-MethyltransferasesPyridazinesPyrimidinescryo-EMpIClnPRMT5prostate cancerprotein-protein interaction inhibitor

Identifiers

PMID42710907
PMCPMC13556114

What OpenQuestion holds

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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.