ArticleScientific reports2025
Menin inhibitor MI-503 exhibits potent anti-cancer activity in osteosarcoma.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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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.
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Who cites it
1 citing paper in PubMed.
- Exosomal Gene Biomarkers in Osteosarcoma: Mifepristone as a Targeted Therapeutic Revealed by Multi-Omics Analysis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
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Authors and funding
6 authors.
Funding
Abstract
Small molecule Menin inhibitor recently has emerged as a new therapeutic by targeting the interaction of histone methyltransferase MLL1 (KMT2A) with Menin. MLL1 is associated with aggressive osteosarcoma (OS) in young adults. The purpose of the study is to explore whether Menin inhibitors have therapeutic effects in OS.To investigate the anti-OS activity of the Menin inhibitor MI-503 in vitro, we performed CCK-8 cell growth and colony formation assay. Cellular thermal shift assay was used to test whether MI-503 binds to Menin in osteosarcoma cells. The expression of oncogenes in MI-503 treated cells were detected by western blotting and Quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. Finally, we established the OS subcutaneous xenograft mice model to study the anti-OS effect of MI-503 in vivo.The results showed that MI-503 dose-dependently suppressed cell proliferation in 6 OS cell lines, including 143B, HOS, Saos-2, SKES1, MG-63, and U2OS. 143B is the most sensitive cell line with EC50 value 0.13 µM. Cellular thermal shift assay showed that MI-503 binds cellular Menin. RT-qPCR assay showed that MI-503 suppressed the expression of Mcl-1 and c-Myc in 143B cells. Western blotting result showed that MI-503 markedly suppressed the H3K4 methylation, significantly suppressed the expression of Mcl-1 and c-Myc, and increased the expression of p27 and cl-PARP in 143B and Saos-2 cells. In a study with 143B cell-derived xenograft model, we found that MI-503 profoundly inhibited OS tumor growth in mice. Immunohistochemistry (IHC) study showed that MI-503 suppressed the H3K4 methylation and inhibited the expression of the cell proliferation biomarker Ki67 in 143B OS xenograft tissue.Overall, our findings demonstrated the potent anti-OS activity of MI-503 in both in vitro and in vivo models, which also indicated that Menin inhibitor may be a prospective therapeutic strategy for human OS.
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