ReviewInternational immunopharmacology2021
Leflunomide an immunomodulator with antineoplastic and antiviral potentials but drug-induced liver injury: A comprehensive review.
Review in International immunopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Lipophagy: A key regulator in oxidative stress and metabolic disorders.Genes & diseases · 2026Review
- Article
- Drug Repurposing as a Broad-Spectrum Strategy Against Coronaviruses: Frontiers in Mechanisms and Clinical Translation.Viruses · 2026Review
- A comprehensive review on thermo-responsive targeted and functional therapy for management of rheumatoid arthritis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- DHODH inhibition suppresses cutaneous squamous cell carcinoma growth by the induction of differentiation through perturbation of the cellular redox balance.Cell death & disease · 2026Article
- Praziquantel ameliorates leflunomide-induced nephrotoxicity in mice: a novel therapeutic approach targeting TGF-β/Smad/Wnt/β-catenin/NF-κB/PPAR-γ signaling and Nrf-2.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Integrating genetic, epigenetic, and clinical signatures via machine learning for robust prediction of leflunomide response in rheumatoid arthritis: a multi-center validation study.Frontiers in immunology · 2026Article
- Clinical characteristics and risk factors of severe myelosuppression in rheumatoid arthritis patients with csDMARD non-adherence: a case series.Frontiers in pharmacology · 2026Review
- Recent Advancement in Drug Delivery Systems for the Treatment of Rheumatoid Arthritis.Current drug discovery technologies · 2026Review
- Integrative biochemical and computational analysis of leflunomide-induced redox alterations in Nauphoeta cinerea.Scientific reports · 2025Article
- NK-A 17E-233I: a novel competitive inhibitor of human dihydroorotate dehydrogenase (DHODH) for cancer therapy.Journal of experimental & clinical cancer research : CR · 2025Article
- Impact of Disease-Modifying Antirheumatic Drugs on Cognitive Function in Older Adults with Rheumatoid Arthritis.Drugs & aging · 2025Review
- Drug Repurposing and Nanotechnology for Topical Skin Cancer Treatment: Redirecting toward Targeted and Synergistic Antitumor Effects.ACS pharmacology & translational science · 2025Review
- Leflunomide-Induced Weight Loss: Involvement of DAHPS Activity and Synthesis of Aromatic Amino Acids.Metabolites · 2024Article
- A review of immune modulators and immunotherapy in infectious diseases.Molecular and cellular biochemistry · 2024Review
- Treating Cardiovascular Disease in the Inflammatory Setting of Rheumatoid Arthritis: An Ongoing Challenge.Biomedicines · 2024Review
- Teriflunomide/leflunomide synergize with chemotherapeutics by decreasing mitochondrial fragmentation via DRP1 in SCLC.iScience · 2024Article
- Safety and Tolerability of KIO-101 Eye Drops in Healthy Volunteers and Patients with Ocular Surface Disease-A Phase I Study.Pharmaceutics · 2024Article
- Novel Therapeutic Hybrid Systems Using Hydrogels and Nanotechnology: A Focus on Nanoemulgels for the Treatment of Skin Diseases.Gels (Basel, Switzerland) · 2024Review
- Approaches Towards Better Immunosuppressive Agents.Current topics in medicinal chemistry · 2024Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leflunomide (LF) represents the prototype member of dihydroorotate dehydrogenase (DHODH) enzyme inhibitors. DHODH is a mitochondrial inner membrane enzyme responsible for catalytic conversion of dihydroorotate into orotate, a rate-limiting step in the de novo synthesis of the pyrimidine nucleotides. LF produces cellular depletion of pyrimidine nucleotides required for cell growth and proliferation. Based on the affected cells the outcome can be attainable as immunosuppression, antiproliferative, and/or the recently gained attention of the antiviral potentials of LF and its new congeners. Also, protein tyrosine kinase inhibition is an additional mechanistic benefit of LF, which inhibits immunological events such as cellular expansion and immunoglobulin production with an enhanced release of immunosuppressant cytokines. LF is approved for the treatment of autoimmune arthritis of rheumatoid and psoriatic pathogenesis. Also, LF has been used off-label for the treatment of relapsing-remitting multiple sclerosis. However, LF antiviral activity is repurposed and under investigation with related compounds under a phase-I trial as a SARS CoV-2 antiviral in cases with COVID-19. Despite success in improving patients' mobility and reducing joint destruction, reported events of LF-induced liver injury necessitated regulatory precautions. LF should not be used in patients with hepatic impairment or in combination with drugs elaborating a burden on the liver without regular monitoring of liver enzymes and serum bilirubin as safety biomarkers. This study aims to review the pharmacological and safety profile of LF with a focus on the LF-induced hepatic injury from the perspective of pathophysiology and possible protective agents.
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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.