ArticleMolecular therapy. Nucleic acids2012
Pharmacokinetics and Toxicity in Rats and Monkeys of coDbait: A Therapeutic Double-stranded DNA Oligonucleotide Conjugated to Cholesterol.
Article in Molecular therapy. Nucleic acids, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 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.
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Who cites it
8 citing papers in PubMed.
- Delivery of oligonucleotides to bone marrow to modulate ferrochelatase splicing in a mouse model of erythropoietic protoporphyria.Nucleic acids research · 2020Article
- Combining the DNA Repair Inhibitor Dbait With Radiotherapy for the Treatment of High Grade Glioma: Efficacy and Protein Biomarkers of Resistance in Preclinical Models.Frontiers in oncology · 2019Article
- First-in-human phase I study of the DNA-repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma.British journal of cancer · 2016Article
- Article
- Sensitive Fibre-Based Thermoluminescence Detectors for High Resolution In-Vivo Dosimetry.Scientific reports · 2015Article
- A preclinical study combining the DNA repair inhibitor Dbait with radiotherapy for the treatment of melanoma.Neoplasia (New York, N.Y.) · 2014Article
- Kinesin KIFC1 actively transports bare double-stranded DNA.Nucleic acids research · 2013Article
- Distribution and radiosensitizing effect of cholesterol-coupled Dbait molecule in rat model of glioblastoma.PloS one · 2012Article
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased DNA repair activity in cancer cells is one of their primary mechanisms of resistance to current radio- and chemotherapies. The molecule coDbait is the first candidate in a new class of drugs that target the double-strand DNA break repair pathways with the aim of overcoming these resistances. coDbait is a 32-base pair (bp) double-stranded DNA molecule with a cholesterol moiety covalently attached to its 5'-end to facilitate its cellular uptake. We report here the preclinical pharmacokinetic and toxicology studies of subcutaneous coDbait administration in rodents and monkeys. Maximum plasma concentration occurred between 2 to 4 hours in rats and at 4 hours in monkeys. Increase in mean AUC0-24h was linear with dose reaching 0.5 mg·h/ml for the highest dose injected (32 mg) for both rats and monkeys. No sex-related differences in maximum concentration (Cmax) nor AUC0-24h were observed. We extrapolated these pharmacokinetic results to humans as the subcutaneous route has been selected for evaluation in clinical trials. Tri-weekly administration of coDbait (from 8 to 32 mg per dose) for 4 weeks was overall well tolerated in rats and monkeys as no morbidity/mortality nor changes in clinical chemistry and histopathology parameters considered to be adverse effects have been observed.
Identifiers
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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.