ArticleBritish journal of cancer2025
Novel Skp1 inhibitor has potent preclinical efficacy against castration-resistant prostate cancer.
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.
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Who cites it
2 citing papers in PubMed.
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Structure-Based Virtual Screening of New Skp1 Inhibitor Chemotypes Targeting F-Box Binding Interface.Drug design, development and therapy · 2026Article
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Authors and funding
23 authors.
Funding
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.
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