Trial reportInvestigational new drugs2003
Phase I and pharmacologic study of the human DNA methyltransferase antisense oligodeoxynucleotide MG98 given as a 21-day continuous infusion every 4 weeks.
Trial report in Investigational new drugs, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 90 citations in OpenAlex.
- Phase II trial of DNA methyltransferase 1 inhibition with the antisense oligonucleotide MG98 in patients with metastatic renal carcinoma: a National Cancer Institute of Canada Clinical Trials Group investigational new drug study.Investigational new drugs · 2006Trial
- Meta-analysis of adverse events in clinical studies with antisense oligonucleotide therapies.Molecular therapy. Nucleic acids · 2026Review
- Epigenetic regulators in cancer therapy and progression.NPJ precision oncology · 2025Review
- Targeting the epigenome with advanced delivery strategies for epigenetic modulators.Bioengineering & translational medicine · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends.Journal of biomedical science · 2021Review
- DNA methylation inhibitors: Retrospective and perspective view.Advances in cancer research · 2021Article
- Epigenetic Mechanisms in DNA Double Strand Break Repair: A Clinical Review.Frontiers in molecular biosciences · 2021Review
- Review
- Epidrug Repurposing: Discovering New Faces of Old Acquaintances in Cancer Therapy.Frontiers in oncology · 2020Review
- DNA Methylation Targeting: The DNMT/HMT Crosstalk Challenge.Biomolecules · 2017Review
- The emerging nexus of active DNA demethylation and mitochondrial oxidative metabolism in post-mitotic neurons.International journal of molecular sciences · 2014Review
- Use of epigenetic drugs in disease: an overview.Genetics & epigenetics · 2014Review
- DNA-intercalators causing rapid re-expression of methylated and silenced genes in cancer cells.Oncotarget · 2013Article
- Trials with 'epigenetic' drugs: an update.Molecular oncology · 2012Review
- Mutations in epigenetic modifiers in myeloid malignancies and the prospect of novel epigenetic-targeted therapy.Advances in hematology · 2012Article
- An overview of epigenetics and chemoprevention.FEBS letters · 2011Review
- Epigenetic aberrations during oncogenesis.Cellular and molecular life sciences : CMLS · 2011Review
- Genetic and epigenetic changes in human prostate cancer.Iranian Red Crescent medical journal · 2011Article
- Epigenetic therapy for breast cancer.International journal of molecular sciences · 2011Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeMG98 is a second generation phosphorothioate antisense oligodeoxynucleotide which is a highly specific inhibitor of translation of the mRNA for human DNA MeTase I (DNMT 1). This phase I study examined the toxicity and pharmacologic profile of MG98 administered as a continuous 21-day intravenous infusion every 4 weeks. PATIENTS AND
methodsFourteen patients with solid cancers received a total of 25 cycles of MG98 at doses ranging from 40 to 240 mg/m2/day. Steady-state concentrations of MG98 were measured as were several pharmacodynamic assessments including mRNA of the target gene, DNMT1, in PBMC. In addition, other potential surrogate markers of drug effects were explored, including hemoglobin F, Vimentin and GADD45.
resultsDose limiting effects were drug-related reversible transaminase elevation and fatigue seen at doses of 240, 200 and 160 mg/m2/day. The dose level of 80 mg/m2/day was felt to be safe and tolerable when delivered on this schedule. No evidence of antitumor activity was observed. Although pharmacokinetic analysis revealed that at the higher dose levels, mean Css values of MG98 were approximately 10-fold times the IC50 values associated with target inhibition in vitro, the extent of MG98 penetration into target tumors in this trial was not determined. No consistent, dose-related changes in correlative markers including DNMT1 mRNA, hemoglobin F, Vimentin and GADD45, were observed.
conclusionsThis schedule of MG98 given as a 21-day continuous intravenous infusion every 4 weeks was poorly tolerated in the highest doses; therefore, further disease-site specific evaluation of the efficacy of this agent will utilize a more favorable, intermittent dosing schedule. Pharmacodynamic evaluations undertaken in an attempt to explore and validate the biological mechanisms of MG98 did not show dose-related effects.
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What OpenQuestion holds
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.