ArticleJournal of experimental & clinical cancer research : CR2025
FL496, an FL118-derived small molecule, induces growth inhibition, senescence, and apoptosis of malignant pleural mesothelioma (MPM) cells, and exhibits anti-MPM tumor efficacy strikingly superior to the pemetrexed-cisplatin combination.
Article in Journal of experimental & clinical cancer research : CR, 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.
- DDX5 (p68) and UbE2T as emerging superior cancer therapeutic targets: dual molecular glue target degradation by FL118 for conquering difficult-to-treat cancers.Journal of experimental & clinical cancer research : CR · 2026Review
- Article
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Authors and funding
11 authors.
Funding
Abstract
backgroundMalignant pleural mesothelioma (MPM) responds poorly to chemotherapy and is a highly progressive malignancy with a median survival time of only 6-9 months. Therefore, the development of anti-MPM tumor agents with high efficacy and low toxicity is urgent and addresses an unmet need for MPM patients.
methodsMedicinal chemistry synthesis of small molecules based on the FL118 drug platform were further comparatively investigated using multiple MPM and osteosarcoma cell/tumor in vitro and/or in vivo models. The method includes cell viability assay, Western blot analysis, colony formation assay, immunocytochemical staining, β-galactosidase senescence staining, flow cytometry, DNA fragmentation cell death detection, vector-free CRISPR-Cas9-mediated gene knockout, bioinformatic analysis, FL496 efficacy determination using severe combined immunodeficiency (SCID) mice with human MPM tumor, and immunohistochemistry (IHC) analysis of MPM tumors.
resultsHere, we report that we identified a novel FL118-derived small molecule (FL496). FL496 appears to be strikingly more effective in inhibiting MPM tumor growth in MPM tumor animal models than the currently most prevalent pemetrexed-cisplatin combination in the clinic. The treatment of MPM cells with FL496 rapidly induced p53 and p21 accumulation, and Rb and p-Rb inhibition, which were associated with MPM cell senescence and G
conclusionsTogether, these results indicate that FL496 is a promising anti-MPM small molecule, and its high anti-MPM potential is worthy of being further explored as a monotherapeutic agent to treat MPM patients in clinical trials.
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