5-Azacytidine

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5-Azacytidine
Systematic (IUPAC) name
4-amino-1-[3,4-dihydroxy-5- (hydroxymethyl) oxolan-2-yl] -1,3,5-triazin-2-one
Identifiers
CAS number	320-67-2
ATC code	?
PubChem	9444
DrugBank	APRD00809
Chemical data
Formula	C₈H₁₂N₄O₅
Mol. mass	244.205 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

5-Azacytidine or 5-aza-2’-deoxycytidine is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Cells in the presence of 5-azacytidine incorporate it into DNA during replication and RNA during transcription. The incorporation of 5-azacytidine into DNA or RNA inhibits methyltransferase thereby causing demethylation in that sequence, affecting the way that cell regulation proteins are able to bind to the DNA/RNA substrate. Inhibition of DNA occurs through the formation of stable complexes between the molecule and with DNA methyltransferases, thereby saturating the cells methylation machinery.

The demethylating agent 5-azacytidine and its deoxy derivative 5-aza-2'deoxycytidine were first synthesized in Czechoslovakia as potential chemotherapeutic agents for cancer.^[1]

It can be used in vitro to remove methyl groups from DNA. This may weaken the effects of gene silencing mechanisms that occurred prior to the methylation. Methylation events are therefore believed to secure the DNA in a silenced state. Demethylation may reduce the stability of silencing signals and thus confer relative gene activation.^[2] 5-azacytidine is mainly used in the treatment of myelodysplastic syndrome. It is marketed as Vidaza.

[edit] References

^ Cihák A (1974). "Biological effects of 5-azacytidine in eukaryotes". Oncology 30 (5): 405-22. PMID 4142650.
^ Whitelaw E and Garrick D (2005), The Epigenome, Chapter 7, In: Mammalian Genomics, Ed: Ruvinsky A & Marshall Graves JA, CABI Publising, Wallingford, UK, ISBN 0851999107.