ArticleClinical epigenetics2019
Novel prodrugs of decitabine with greater metabolic stability and less toxicity.
Article in Clinical epigenetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Incorporation of Organosilicon Motifs in Natural and Synthetic Small Molecules for Anticancer Therapeutics: Current Perspectives and Future Opportunities in Drug Design.Molecules (Basel, Switzerland) · 2026Review
- Orally available decitabine prodrug OR-2100 induces mitotic perturbation for the treatment of double-hit lymphoma.Blood neoplasia · 2025Article
- Helicobacter pylori-induced aberrant methylation of ID4 mediated by DNMT3B drives gastric cancer progression via DEC1-SHH signaling pathway.Cell death & disease · 2025Article
- Review
- The Underlying Mechanisms and Emerging Strategies to Overcome Resistance in Breast Cancer.Cancers · 2025Review
- Epigenetic agents, zebularine and valproic acid, inhibit the growth of the oral squamous cell carcinoma cell line HSC4 in vitro and in vivo.Discover oncology · 2025Article
- Treating Hematological Malignancies With OR-2100, an Orally Bioavailable Prodrug of Decitabine.Cancer science · 2025Review
- Epigenetic drugs in cancer therapy.Cancer metastasis reviews · 2025Review
- Promoter hypermethylation of SFRP1 is an allele fraction-dependent prognostic biomarker in metastatic pancreatic ductal adenocarcinoma.Frontiers in oncology · 2025Article
- SFRP1 mediates cancer-associated fibroblasts to suppress cancer cell proliferation and migration in head and neck squamous cell carcinoma.BMC cancer · 2024Article
- Review
- Study of the effect of sFRP1 protein on molecules involved in the regulation of DNA methylation in CML cell line.Medical oncology (Northwood, London, England) · 2024Article
- Article
- Role of DNA methylation during recovery from spinal cord injury with and without βExperimental neurology · 2023Article
- Combined inhibition of histone deacetylase and cytidine deaminase improves epigenetic potency of decitabine in colorectal adenocarcinomas.Clinical epigenetics · 2023Article
- Dual targeting of aberrant DNA and histone methylation synergistically suppresses tumor cell growth in ATL.Blood advances · 2023Article
- Epigenetic drugs in somatostatin type 2 receptor radionuclide theranostics and radiation transcriptomics in mouse pheochromocytoma models.Theranostics · 2023Article
- The H2A.Z-KDM1A complex promotes tumorigenesis by localizing in the nucleus to promote SFRP1 promoter methylation in cholangiocarcinoma cells.BMC cancer · 2022Article
- Adult T-cell leukemia-lymphoma acquires resistance to DNA demethylating agents through dysregulation of enzymes involved in pyrimidine metabolism.International journal of cancer · 2022Article
- A Novel Cognition of Decitabine: Insights into Immunomodulation and Antiviral Effects.Molecules (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDNA demethylation therapy is now used in practice for hematological tumors and is being developed for solid tumors. Nevertheless, it is difficult to achieve stable pharmacokinetics with the current DNA-demethylating agents, azacitidine (AZA) and decitabine (DAC), because of their rapid deamination by cytidine deaminase in vivo and spontaneous hydrolytic cleavage. Here, we aimed to develop metabolically stable prodrugs of AZA and DAC as novel DNA-demethylating agents.
resultsThirty-five 5'-O-trialkylsilylated AZAs/DACs were synthesized with potential resistance to deamination. Out of these, 11 compounds exhibited demethylating activity similar to that of DAC and guadecitabine, and a suitable aqueous solubility. Pharmacokinetic analysis in mice showed that OR-2003 displayed the highest serum concentration and the area under the curve in an intraperitoneal experiment, whereas OR-2100 exhibited high stability to cytidine deaminase. Treatment of cells with OR-2003 and OR-2100 depleted DNA methyltransferase 1 completely and induced both gene-specific and genome-wide demethylation. The treatment suppressed the growth of multiple types of cancer cells and induced re-expression of tumor suppressor genes. The anti-tumor effect and DNA demethylation effect of OR-2003 and OR-2100 were comparable to that of DAC with fewer adverse effects in vivo.
conclusionsWe developed two novel prodrugs of DAC that exhibited greater stability, comparable DNA demethylation activity, and less toxicity. These compounds are expected to overcome the difficulty in achieving stable pharmacokinetics in patients, leading to maximum DNA demethylation activity with minimum adverse effects.
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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.