Evidence map›Paper›PMID 40253488›Full record

ArticleBritish journal of cancer2025

Novel Skp1 inhibitor has potent preclinical efficacy against castration-resistant prostate cancer.

Xin Li, Kenza Mamouni, Rui Zhao, Lijuan Bai, Yanhua Chen, Yifei Wu, Zhong-Ru Xie, Giuseppe A Sautto, Degang Liu, Nathan J Bowen and 13 more

Abstract read
In one paragraph

Article in British journal of cancer, 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

23 authors.

Xin LiCenter for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, Atlanta, GA, USA.
Kenza MamouniMolecular Oncology and Biomarkers Program, Georgia Cancer Center; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Rui ZhaoMolecular Oncology and Biomarkers Program, Georgia Cancer Center; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Lijuan BaiMolecular Oncology and Biomarkers Program, Georgia Cancer Center; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Yanhua ChenMolecular Oncology and Biomarkers Program, Georgia Cancer Center; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA, USA.
Yifei WuSchool of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA, USA.
Zhong-Ru XieSchool of Electrical and Computer Engineering, College of Engineering, University of Georgia, Athens, GA, USA.
Giuseppe A SauttoFlorida Research and Innovation Center, Cleveland Clinic, Port St, Lucie, FL, USA.ORCID http://orcid.org/0000-0002-0273-2235
Degang LiuSartorius Corporation, Bohemia, NY, USA.
Nathan J BowenCenter for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, Atlanta, GA, USA.
Alira DanaherCenter for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, Atlanta, GA, USA.
Dehong LiCenter for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, Atlanta, GA, USA.
Nicholas CookCenter for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, Atlanta, GA, USA.
Skylar GraysonCenter for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, Atlanta, GA, USA.
Jedidiah ZhuCenter for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, Atlanta, GA, USA.
Ilsa M ColemanDivision of Human Biology, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA.
Peter S NelsonDivision of Human Biology, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-5451-5726
Qichao BaoChemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, USA.
Jia ZhouChemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, USA.
Adeboye O OsunkoyaDepartment of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
Omer KucukDepartment of Urology, Emory University School of Medicine, Atlanta, GA, USA.
Lajos GeraDepartment of Biochemistry and Molecular Genetics, University of Colorado Denver, Anschutz Medical Campus, School of Medicine, Aurora, CO, USA. Lajos.gera@cuanschutz.edu.
Daqing WuCenter for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, Atlanta, GA, USA. dwu@cau.edu.ORCID http://orcid.org/0000-0001-9050-7793

Funding

TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI John Kyung Lee · 2002 to 2026
$58.1M
To Investigate Molecular Mechanisms of Aging-Related Growth of the Prostate - Implications in Prostate Tumorigenesis and Cancer TreatmentU54MD007590 · NIMHD · CLARK ATLANTA UNIVERSITY · PI DAQING WU · 2019 to 2026
$17.1M
Technologies/Resources for Core LaboratoriesG12MD007590 · NIMHD · CLARK ATLANTA UNIVERSITY · PI KHAN, SHAFIQ A · 2012 to 2018
$7.6M
Targeting chemoresistant prostate cancer with novel EED inhibitorsR01CA256058 · NCI · CLARK ATLANTA UNIVERSITY · PI DAQING WU · 2022 to 2026
$2.1M
Targeting Vulnerabilities Exposed by Cancer Treatment-Induced Lineage PlasticityR01CA266452 · NCI · FRED HUTCHINSON CANCER CENTER · PI PETER S NELSON · 2022 to 2026
$2.0M
Small-molecule therapy for metastatic castration-resistant prostate cancerR42CA217491 · NCI · METCURE THERAPEUTICS, LLC · PI WU, DAQING · 2021 to 2022
$1.9M
Research Specialist in Cancer Genomics to Integrate Basic Research and Clinical DataR50CA274336 · NCI · FRED HUTCHINSON CANCER CENTER · PI ILSA COLEMAN · 2023 to 2026
$452k
A Prostate Cancer Dependency Map to Identify Tumor Subtype-Specific VulnerabilitiesR21CA277368 · NCI · FRED HUTCHINSON CANCER CENTER · PI NELSON, PETER S · 2023 to 2024
$442k
NCI NIH HHS P50 CA097186NCI NIH HHS R01 CA256058NCI NIH HHS R01 CA266452NCI NIH HHS R21 CA277368NCI NIH HHS R42 CA217491NCI NIH HHS R50 CA274336NIMHD NIH HHS G12 MD007590NIMHD NIH HHS U54 MD007590U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) P50CA097186U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA256058U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R21CA277368U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R42CA217491U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R50CA274336
6 · The paper itself

Abstract

backgroundMetastatic, castration-resistant prostate cancer (mCRPC) directly contributes to the mortality and morbidity of prostate cancer. It is imperative to identify new molecular targets and discover effective therapeutic agents against lethal mCRPC.

methodsThe anticancer activities and mechanism of action of the small-molecule lead compound were investigated in preclinical models of human prostate cancer. Immunohistochemistry was employed to determine the expression of S-phase kinase-associated protein 1 (Skp1) in human prostate tissues.

resultsGH501 demonstrates nanomolar potency in the NCI-60 human cancer cell panel and multiple mCRPC cell lines with diverse genetic backgrounds, including those resistant to androgen deprivation therapy drugs. Mechanistically, GH501 may bind Skp1 and disrupt the physical interaction between Skp1 and S-phase kinase-associated protein 2 (Skp2) within the Skp1-Cullin1-F-box protein ubiquitin ligase complexes (SCF), thereby affecting multiple oncogenic signals implicated in mCRPC progression, including p21, p27, β-catenin, cyclin D1, enhancer of zeste homolog 2 (EZH2), c-Myc, and survivin. GH501 exhibits excellent in vitro and in vivo safety pharmacology, and GH501 monotherapy effectively inhibits the in vivo growth of cell- and patient-derived xenografts in intraosseous and subcutaneous models. Skp1 expression is significantly increased in human prostate cancer specimens.

conclusionThese results indicate that interrupting Skp1-Skp2 interaction is an effective approach to target mCRPC and warrant further preclinical development of GH501 as a promising therapeutic candidate.

Indexed as

Antineoplastic AgentsProstatic Neoplasms, Castration-ResistantS-Phase Kinase-Associated ProteinsAnimalsCell Line, TumorCell ProliferationHumansMaleMiceXenograft Model Antitumor AssaysAntineoplastic AgentsSKP1 protein, humanSKP2 protein, humanS-Phase Kinase-Associated Proteins

Identifiers

PMID40253488
PMCPMC12152123

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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.