ArticleOncogene2019
Selective inhibition of mutant IDH1 by DS-1001b ameliorates aberrant histone modifications and impairs tumor activity in chondrosarcoma.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 67 citations in OpenAlex.
- Proof of Concept of the Radiosensitizing Effect of Gadolinium Oxide Nanoparticles in Cell Spheroids and a Tumor-Implanted Murine Model of Chondrosarcoma.International journal of nanomedicine · 2022Trial
- Review
- Long-term administration of the mutant IDH inhibitor DS-1001b suppresses the growth of IDH1-mutant glioma in vitro and in mouse xenograft models and alters epigenetic profiles.Acta neuropathologica · 2026Article
- Machine learning-based QSAR and structure-based virtual screening guided discovery of novel mIDH1 inhibitors from natural products.Journal of computer-aided molecular design · 2025Article
- Review
- Antcin K inhibits chondrosarcoma motility by reducing MMP‑7 expression via downregulation of the PI3K, Akt, mTOR and NF‑κB signaling pathway.Molecular medicine reports · 2025Article
- Phase I Study of the Mutant IDH1 Inhibitor Ivosidenib: Long-term Safety and Clinical Activity in Patients with Conventional Chondrosarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Establishment and characterization of TK-DDCS1: a novel IDH1 mutated dedifferentiated chondrosarcoma cell line.Human cell · 2025Article
- Discovery of HMPL-306 (Ranosidenib), a New Potent and Selective Dual Inhibitor of Mutant IDH1 and 2 in Clinical Development for Cancer Treatment.ACS medicinal chemistry letters · 2025Article
- Essential role of the metabolite α-ketoglutarate in bone tissue and bone-related diseases.Acta biochimica et biophysica Sinica · 2025Review
- Chondrosarcoma: New Molecular Insights, Challenges in Near-Patient Preclinical Modeling, and Therapeutic Approaches.International journal of molecular sciences · 2025Review
- IDH1/2 Mutations in Cancer: Unifying Insights and Unlocking Therapeutic Potential for Chondrosarcoma.Targeted oncology · 2025Review
- Targeting Isocitrate Dehydrogenase (IDH) in Solid Tumors: Current Evidence and Future Perspectives.Cancers · 2024Review
- High expression of BCAT1 sensitizes AML cells to PARP inhibitor by suppressing DNA damage response.Journal of molecular medicine (Berlin, Germany) · 2024Article
- The curious case of IDH mutant acute myeloid leukaemia: biochemistry and therapeutic approaches.Biochemical Society transactions · 2023Review
- Review
- Mutant IDH regulates glycogen metabolism from early cartilage development to malignant chondrosarcoma formation.Cell reports · 2023Article
- Molecular In-Depth Characterization of Chondrosarcoma for Current and Future Targeted Therapies.Cancers · 2023Review
- Regulative Roles of Metabolic Plasticity Caused by Mitochondrial Oxidative Phosphorylation and Glycolysis on the Initiation and Progression of Tumorigenesis.International journal of molecular sciences · 2023Review
- The regulatory mechanisms and inhibitors of isocitrate dehydrogenase 1 in cancer.Acta pharmaceutica Sinica. B · 2023Review
Corrections and comments
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Authors and funding
28 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chondrosarcoma is the second most common malignant bone tumor. It is characterized by low vascularity and an abundant extracellular matrix, which confer these tumors resistance to chemotherapy and radiotherapy. There are currently no effective treatment options for relapsed or dedifferentiated chondrosarcoma, and new targeted therapies need to be identified. Isocitrate dehydrogenase (IDH) mutations, which are detected in ~50% of chondrosarcoma patients, contribute to malignant transformation by catalyzing the production of 2-hydroxyglutarate (2-HG), a competitive inhibitor of α-ketoglutarate-dependent dioxygenases. Mutant IDH inhibitors are therefore potential novel anticancer drugs in IDH mutant tumors. Here, we examined the efficacy of the inhibition of mutant IDH1 as an antitumor approach in chondrosarcoma cells in vitro and in vivo, and investigated the association between the IDH mutation and chondrosarcoma cells. DS-1001b, a novel, orally bioavailable, selective mutant IDH1 inhibitor, impaired the proliferation of chondrosarcoma cells with IDH1 mutations in vitro and in vivo, and decreased 2-HG levels. RNA-seq analysis showed that inhibition of mutant IDH1 promoted chondrocyte differentiation in the conventional chondrosarcoma L835 cell line and caused cell cycle arrest in the dedifferentiated JJ012 cell line. Mutant IDH1-mediated modulation of SOX9 and CDKN1C expression regulated chondrosarcoma tumor progression, and DS-1001b upregulated the expression of these genes via a common mechanism involving the demethylation of H3K9me3. DS-1001b treatment reversed the epigenetic changes caused by aberrant histone modifications. The present data strongly suggest that inhibition of mutant IDH1 is a promising therapeutic approach in chondrosarcoma, particularly for the treatment of relapsed or dedifferentiated chondrosarcoma.
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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.