Zebularine is a
nucleoside analog
Nucleoside analogues are nucleosides which contain a nucleic acid analogue and a sugar. Nucleotide analogs are nucleotides which contain a nucleic acid analogue, a sugar, and a phosphate group with one to three phosphates.
Nucleoside and nucl ...
of
cytidine
Cytidine (symbol C or Cyd) is a nucleoside molecule that is formed when cytosine is attached to a ribose ring (also known as a ribofuranose) via a β-N1-glycosidic bond. Cytidine is a component of RNA. It is a white water-soluble solid. which is ...
. It is a
transition state analog Transition state analogs (transition state analogues), are chemical compounds with a chemical structure that resembles the transition state of a substrate molecule in an enzyme-catalyzed chemical reaction. Enzymes interact with a substrate by mean ...
inhibitor of
cytidine deaminase by binding to the active size as covalent hydrates. Also shown to inhibit
DNA methylation
DNA methylation is a biological process by which methyl groups are added to the DNA molecule. Methylation can change the activity of a DNA segment without changing the sequence. When located in a gene promoter, DNA methylation typically acts ...
and tumor growth both in vitro and in vivo.
In a small study of mice with a defective ''
Adenomatous polyposis coli
Adenomatous polyposis coli (APC) also known as deleted in polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the ''APC'' gene. The APC protein is a negative regulator that controls beta-catenin concentrations and interacts with ...
'' gene, oral administration of zebularine to males had no effect on the overall methylation of DNA or the number of polyps, but in females the average number of polyps was reduced from 58 to 1. It has therefore been suggested for drug use as a prototype of
epigenetic therapy
Epigenetic therapy is the use of drugs or other epigenome-influencing techniques to treat medical conditions. Many diseases, including cancer, heart disease, diabetes, and mental disorder, mental illnesses are influenced by epigenetic mechanisms. ...
for cancer
chemoprevention
Chemoprevention (also chemoprophylaxis) refers to the administration of a medication for the purpose of preventing disease or infection. Antibiotics, for example, may be administered to patients with disorders of immune system function to prevent b ...
.
References
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Nucleosides
Pyrimidones