Evidence map›Paper›PMID 41939427›Full record

ArticleDrug design, development and therapy2026

Structure-Based Virtual Screening of New Skp1 Inhibitor Chemotypes Targeting F-Box Binding Interface.

Muzammal Hussain, Yongzhi Lu, Gui-Zhen Wang, Muqddas Tariq, Jiancun Zhang, Guang-Biao Zhou, Jinsong Liu

Abstract read
In one paragraph

Article in Drug design, development and therapy, 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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1 · What the graph read from it

What it found

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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

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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

7 authors.

Muzammal HussainCenter for Chemical Biology and Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, People's Republic of China.ORCID 0000-0002-1117-5864
Yongzhi LuCenter for Chemical Biology and Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, People's Republic of China.
Gui-Zhen WangState Key Laboratory of Molecular Oncology and Department of Internal Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Muqddas TariqCenter for Chemical Biology and Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, People's Republic of China.ORCID 0009-0008-4403-5906
Jiancun ZhangCenter for Chemical Biology and Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, People's Republic of China.
Guang-Biao ZhouState Key Laboratory of Molecular Oncology and Department of Internal Medicine, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
Jinsong LiuCenter for Chemical Biology and Drug Discovery, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, People's Republic of China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Skp1 is a potential pharmacological target for cancer treatment. However, the few Skp1 inhibitors reported to date have exhibited limited structural diversity and target specificity. This highlights the need for new chemical scaffolds that could potentially be developed into potent and specific Skp1 inhibitors. Methods: We performed a large-scale, hierarchical, structure-based virtual screening (SBVS) integrated with molecular dynamics (MD) simulations against a hydrophobic and shallow P1 hotspot region within the F-box binding interface of Skp1, using a commercial compound library (~280,000 compounds). The top-ranked hits were then experimentally validated using in vitro biophysical and biochemical assays, followed by evaluation of cell viability. Results: The SBVS campaign yielded 28 potential hits. Using a thermal stability shift assay (TSA), we confirmed that several compounds directly bind to both full-length Skp1 and its truncated variant containing only the P1 hotspot (Skp1 Conclusion: Compounds #04, #12, and #24 represent interesting scaffolds and may serve as valuable starting points for future structure-activity relationship (SAR) studies aimed at developing a new class of selective Skp1 inhibitors.

Indexed as

Antineoplastic AgentsF-Box ProteinsS-Phase Kinase-Associated ProteinsBinding SitesCell Line, TumorCell ProliferationCell SurvivalDose-Response Relationship, DrugDrug Evaluation, PreclinicalDrug Screening Assays, AntitumorHumansMolecular Dynamics SimulationMolecular StructureStructure-Activity RelationshipAntineoplastic AgentsF-Box ProteinsSKP1 protein, humanS-Phase Kinase-Associated Proteinsbinding free energyhydrophobic hotspotmolecular dockingmolecular dynamics simulationSkp1 inhibitorsvirtual screening

Identifiers

PMID41939427
PMCPMC13049376

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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.