ArticlePloS one2013
Leflunomide reduces proliferation and induces apoptosis in neuroblastoma cells in vitro and in vivo.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 64 citations in OpenAlex.
- Structural Basis for Potent Inhibition of Human DHODH by Quinoline-4-carboxylic Acid Derivatives.ACS omega · 2026Article
- Novel small molecule derivatives improve survivability in the cellular model of Huntington's diseaseRSC medicinal chemistry · 2026Article
- Highlighting the Therapeutic Potential of an Underexplored Target: Human Dihydroorotate Dehydrogenase in Cancer, Rheumatoid Arthritis and Sclerosis.Current topics in medicinal chemistry · 2026Review
- Article
- Multi-omics analysis identifies stemness-driven molecular subtypes, prognostic signature, epigenetic target APCDD1, and drug candidate Leflunomide in Wilms tumor.Frontiers in oncology · 2026Article
- De novo pyrimidine biosynthesis inhibition synergizes with BCL-XNature communications · 2025Article
- Transcriptomic analysis of the anti-tumor effects of leflunomide in prolactinoma.Scientific reports · 2025Article
- Anticancer effect of the antirheumatic drug leflunomide on oral squamous cell carcinoma by the inhibition of tumor angiogenesis.Discover oncology · 2025Article
- Mechanisms of S-phase arrest and mitochondrial dysfunction in complex III by DHODH inhibitors in tumorigenic TNBC cells.Histochemistry and cell biology · 2024Article
- Teriflunomide/leflunomide synergize with chemotherapeutics by decreasing mitochondrial fragmentation via DRP1 in SCLC.iScience · 2024Article
- Leflunomide Treatment Does Not Protect Neural Cells following Oxygen-Glucose Deprivation (OGD) In Vitro.Cells · 2024Article
- An AI Approach to Identifying Novel Therapeutics for Rheumatoid Arthritis.Journal of personalized medicine · 2023Review
- MYCN and Metabolic Reprogramming in Neuroblastoma.Cancers · 2022Review
- Role of pH in Regulating Cancer Pyrimidine Synthesis.Journal of xenobiotics · 2022Review
- UBE2T-mediated Akt ubiquitination and Akt/β-catenin activation promotes hepatocellular carcinoma development by increasing pyrimidine metabolism.Cell death & disease · 2022Article
- Epigenetic landscape of drug responses revealed through large-scale ChIP-seq data analyses.BMC bioinformatics · 2022Article
- Drug repositioning for esophageal squamous cell carcinoma.Frontiers in genetics · 2022Article
- Teriflunomide - The common drug with underestimated oxygen - Dependent anticancer potential.Biochemistry and biophysics reports · 2021Article
- Nitrile-containing pharmaceuticals: target, mechanism of action, and their SAR studies.RSC medicinal chemistry · 2021Review
- Therapeutic targeting of both dihydroorotate dehydrogenase and nucleoside transport in MYCN-amplified neuroblastoma.Cell death & disease · 2021Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leflunomide as an immunosuppressive drug is generally used in the treatment of rheumatoid arthritis. It inhibits DHODH (dihydroorotate dehydrogenase ), which is one of the essential enzymes in the de novo pyrimidine biosynthetic pathway. Here we showed that leflunomide significantly reduced cell proliferation and self-renewal activity. Annexin V-FITC/PI staining assay revealed that leflunomide induced S-phase cell cycle arrest, and promoted cell apoptosis. In vivo xenograft study in SCID mice showed that leflunomide inhibited tumor growth and development. We also observed that DHODH was commonly expressed in neuroblastoma. When treated with leflunomide, the neuroblastoma cell lines BE(2)-C, SK-N-DZ, and SK-N-F1 showed dramatic inhibition of DHODH at mRNA and protein levels. Considering the favorable toxicity profile and the successful clinical experience with leflunomide in rheumatoid arthritis, this drug represents a potential new candidate for targeted therapy in neuroblastoma.
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Registered trials
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.