ArticleCancer chemotherapy and pharmacology2012
Single-dose pharmacokinetic and toxicity analysis of pyrrole-imidazole polyamides in mice.
Article in Cancer chemotherapy and pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Modulation of topoisomerase IIα expression and chemosensitivity through targeted inhibition of NF-Y:DNA binding by a diamino p-anisyl-benzimidazole (Hx) polyamide.Biochimica et biophysica acta. Gene regulatory mechanisms · 2017Article
- [Recognition study of double strand DNA with hairpin oligopolyamide].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2017Article
- Systematic synthetic and biophysical development of mixed sequence DNA binding agents.Organic & biomolecular chemistry · 2017Article
- An HRE-Binding Py-Im Polyamide Impairs Hypoxic Signaling in Tumors.Molecular cancer therapeutics · 2016Article
- Identification of a novel E-box binding pyrrole-imidazole polyamide inhibiting MYC-driven cell proliferation.Cancer science · 2015Article
- Article
- Tumor xenograft uptake of a pyrrole-imidazole (Py-Im) polyamide varies as a function of cell line grafted.Journal of medicinal chemistry · 2014Article
- A C-14 labeled Py-Im polyamide localizes to a subcutaneous prostate cancer tumor.Bioorganic & medicinal chemistry · 2014Article
- Article
- Fluorescent probes for nucleic Acid visualization in fixed and live cells.Molecules (Basel, Switzerland) · 2013Review
- NIR-/pH-Responsive drug delivery of functionalized single-walled carbon nanotubes for potential application in cancer chemo-photothermal therapy.Pharmaceutical research · 2013Article
- Animal toxicity of hairpin pyrrole-imidazole polyamides varies with the turn unit.Journal of medicinal chemistry · 2013Article
- Activity of a Py-Im polyamide targeted to the estrogen response element.Molecular cancer therapeutics · 2013Article
- Antitumor activity of a pyrrole-imidazole polyamide.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Synthesis of cyclic Py-Im polyamide libraries.The Journal of organic chemistry · 2013Article
- DNA damage repair genes controlling human papillomavirus (HPV) episome levels under conditions of stability and extreme instability.PloS one · 2013Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
purposePyrrole-imidazole (Py-Im) polyamides are programmable, sequence-specific DNA minor groove-binding ligands. Previous work in cell culture has shown that various polyamides can be used to modulate the transcriptional programs of oncogenic transcription factors. In this study, two hairpin polyamides with demonstrated activity against androgen receptor signaling in cell culture were administered to mice to characterize their pharmacokinetic properties.
methodsPy-Im polyamides were administered intravenously by tail vein injection. Plasma, urine, and fecal samples were collected over a 24-h period. Liver, kidney, and lung samples were collected postmortem. Concentrations of the administered polyamide in the plasma, excretion, and tissue samples were measured using LC/MS/MS. The biodistribution data were analyzed by both non-compartmental and compartmental pharmacokinetic models. Animal toxicity experiments were also performed by monitoring weight loss after a single subcutaneous (SC) injection of either polyamide.
resultsThe biodistribution profiles of both compounds exhibited rapid localization to the liver, kidneys, and lungs upon injection. Plasma distribution of the two compounds showed distinct differences in the rate of clearance, the volume of distribution, and the AUCs. These two compounds also have markedly different toxicities after SC injection in mice.
conclusionsThe variations in pharmacokinetics and toxicity in vivo stem from a minor chemical modification that is also correlated with differing potency in cell culture. The results obtained in this study could provide a structural basis for further improvement of polyamide activity both in cell culture and in animal models.
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