ArticleAntimicrobial agents and chemotherapy2011
CMX001 (1-O-hexadecyloxypropyl-cidofovir) inhibits polyomavirus JC replication in human brain progenitor-derived astrocytes.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07511049 (Safety and Tolerability of Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy), which is not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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.
Safety and Tolerability of Intravenous Brincidofovir as an Antiviral for Treatment of Progressive Multifocal Leukoencephalopathy: A Pilot Study
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Guidelines for the prevention and treatment of opportunistic infections in HIV-exposed and HIV-infected children: recommendations from the National Institutes of Health, Centers for Disease Control and Prevention, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics.The Pediatric infectious disease journal · 2013Guideline
- A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Oral Brincidofovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2019Trial
- Therapeutic potential of flavonols in the treatment of JCPyV.Microbiology spectrum · 2025Article
- Article
- Brincidofovir Effectively Inhibits Proliferation of Pseudorabies Virus by Disrupting Viral Replication.Viruses · 2024Article
- Large Subunit of the Human Herpes Simplex Virus Terminase as a Promising Target in Design of Anti-Herpesvirus Agents.Molecules (Basel, Switzerland) · 2023Article
- An Elusive Target: Inhibitors of JC Polyomavirus Infection and Their Development as Therapeutics for the Treatment of Progressive Multifocal Leukoencephalopathy.International journal of molecular sciences · 2023Review
- Not a Disease of the Past: A Case Series of Progressive Multifocal Leukoencephalopathy in the Established Antiretroviral Era.AIDS research and human retroviruses · 2019Article
- Magnetic-targeting of polyethylenimine-wrapped iron oxide nanoparticle labeled chondrocytes in a rabbit articular cartilage defect model.RSC advances · 2018Article
- Progressive multifocal leukoencephalopathy: current treatment options and future perspectives.Therapeutic advances in neurological disorders · 2015Review
- Effect of Leflunomide, Cidofovir and Ciprofloxacin on replication of BKPyV in a salivary gland in vitro culture system.Antiviral research · 2015Article
- Brincidofovir (CMX001) inhibits BK polyomavirus replication in primary human urothelial cells.Antimicrobial agents and chemotherapy · 2015Article
- Antiviral effects of artesunate on JC polyomavirus replication in COS-7 cells.Antimicrobial agents and chemotherapy · 2014Article
- Inter- and intralaboratory comparison of JC polyomavirus antibody testing using two different virus-like particle-based assays.Clinical and vaccine immunology : CVI · 2014Article
- Efficacy of recombinant human interleukin 7 in a patient with severe lymphopenia-related progressive multifocal leukoencephalopathy.Open forum infectious diseases · 2014Article
- Highlights in antiviral drug research: antivirals at the horizon.Medicinal research reviews · 2013Review
- Differentiation of human fetal multipotential neural progenitor cells to astrocytes reveals susceptibility factors for JC virus.Journal of virology · 2013Article
- Human polyomavirus reactivation: disease pathogenesis and treatment approaches.Clinical & developmental immunology · 2013Review
- Molecular biology, epidemiology, and pathogenesis of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain.Clinical microbiology reviews · 2012Review
- Progressive multifocal leukoencephalopathy: clinical and molecular aspects.Reviews in medical virology · 2012Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
Polyomavirus JC (JCV) replication causes progressive multifocal leukoencephalopathy (PML), a frequently fatal brain disease in immunodeficient patients, yet antiviral drugs are lacking. We characterized the lipid conjugate 1-O-hexadecyloxypropyl-cidofovir (CMX001) regarding JCV (Mad-4) replication in human brain progenitor-derived astrocytes (PDA) and the simian virus 40 (SV40) large-T-antigen-expressing COS-7 cells up to 7 days postinfection (dpi). We examined JCV loads by PCR, the infection rate by immunofluorescence, and host cell toxicity by WST-1 and BrdU incorporation assays. Supernatants from CMX001-treated PDA demonstrated a drug concentration-dependent decrease in JCV loads and infectivity. CMX001 had only a modest effect on host cell metabolism but reduced overall BrdU incorporation. In PDA at 7 dpi, the CMX001 50% effective concentration (EC50) was 5.55 nM, the 50% cytotoxic concentration (CC50) was 184.6 nM, and the 50% selectivity index (SI50) was 33.3. The EC90 was 19.7 nM, the CC90 was 5,054 nM, and the SI90 was 256.1. In COS-7 cells, JCV replication was faster and the EC50 and EC90 were 18- and 37-fold higher than those in PDA, i.e., 0.1 μM and 0.74 μM (CC50, 0.67 μM; SI50, 6.7; CC90, 12.2 μM; SI90, 16.5) at 5 dpi. We conclude that CMX001 inhibits JCV replication at concentrations in vitro that can be attained by oral administration without significant side effects in clinical studies.
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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.