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Lung Cancer Treatments and Mutations / Ovarian Cancer Diagnosis and Treatment / Cancer Related Gene Regulation · Journal article
Journal of Ovarian Research · September 9, 2026
Early or partial results. Treat as a signal, not a conclusion.
This is a preclinical drug discovery report identifying tepotinib as a LY75-targeting compound with anti-tumor activity in ovarian cancer cell lines and a mouse xenograft model. The study demonstrates preferential inhibition of LY75-high cells and a tumor inhibition rate of 79.6% in vivo, but provides no human clinical data and does not fully exclude off-target MET-inhibitory effects as a mechanism. Further clinical investigation is required before any therapeutic recommendation.
Structure-based virtual screening with in vitro cell-based and in vivo xenograft validation. In vitro: human ovarian cancer cell lines (SKOV3, OVCAR-8, HO8910). In vivo: immunocompromised mice bearing SKOV3 xenografts. Genomic analysis: tissue samples from TCGA and Human Protein Atlas (HPA) public datasets.. Intervention: Tepotinib (small-molecule LY75 inhibitor) administered orally in xenograft studies; in vitro doses varied by assay.. Compared with: LY75-low HO8910 cells as negative control; capmatinib (MET inhibitor) as pharmacological control to assess MET-specific contribution; untreated control xenografts..
Tepotinib showed IC₅₀ values of 16.31 µM (SKOV3) and 18.91 µM (OVCAR-8) in LY75-high ovarian cancer cells Direct binding confirmed with kinetic K_D = 2.52 µM and steady-state K_D = 3.74 µM by SPR Oral tepotinib achieved 79.6% tumor inhibition rate in SKOV3 xenograft model
Source does not report pharmacokinetics, toxicity, or maximum tolerated dose in animals
This preclinical finding does not yet support clinical use. Professionals should regard tepotinib as a candidate compound requiring further mechanistic validation and eventual clinical trials before any therapeutic application in ovarian cancer can be considered.
Preclinical discovery study using virtual screening and in vitro/xenograft models without clinical data; identifies a candidate compound but requires clinical validation.
As stated by the source record.
Quoted from the source exactly as published.
This preclinical finding does not yet support clinical use. Professionals should regard tepotinib as a candidate compound requiring further mechanistic validation and eventual clinical trials before any therapeutic application in ovarian cancer can be considered.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
To identify small-molecule inhibitors targeting LY75 and evaluate their anti-tumor activity and underlying mechanisms in ovarian cancer. LY75 expression and prognostic relevance were analyzed using TCGA and HPA datasets. Structure-based virtual screening of the TargetMol compound library was performed using the LY75 crystal structure (PDB: 8K8H), followed by docking, MM/GBSA, PLIF, and ADMET analyses. Candidate compounds were evaluated by CCK-8, apoptosis, migration, protein stability, SPR binding, and xenograft assays. To address the known MET-inhibitory background of Tepotinib, c-MET expression, MET–LY75 co-expression, and pharmacological controls with capmatinib were assessed. LY75 was significantly upregulated in ovarian cancer tissues and high LY75 expression was associated with shorter progression-free survival. Tepotinib was identified as the leading candidate and preferentially inhibited LY75-high SKOV3 and OVCAR-8 cells, with IC₅₀ values of 16.31 µM and 18.91 µM, respectively, while showing weaker activity in LY75-low HO8910 cells. SPR confirmed direct binding between Tepotinib and LY75 (kinetic K _ D = 2.52 µM; steady-state K _ D = 3.74 µM). Tepotinib induced apoptosis, inhibited migration, and downregulated LY75 protein by accelerating its degradation through a ubiquitin-proteasome-independent mechanism. In vivo, oral Tepotinib markedly suppressed SKOV3 xenograft growth, achieving a tumor inhibition rate of 79.6%, and reduced LY75 expression in tumor tissues. MET-related analyses and capmatinib controls suggested that MET inhibition alone was insufficient to account for the full anti-tumor activity of Tepotinib. This study identifies Tepotinib as a repurposed small molecule with LY75-binding and LY75-downregulating activity in ovarian cancer. These findings support LY75 as a potential therapeutic target and provide a rationale for further investigation of Tepotinib-based targeted therapy in ovarian cancer.
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