Decitabine

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Decitabine
Clinical data
Trade namesDacogen, Demylocan
Other names5-aza-2'-deoxycytidine
AHFS/Drugs.comMonograph
MedlinePlusa608009
License data
Routes of
administration		Intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Protein binding<1%
Elimination half-life30 minutes
Identifiers
  • 4-Amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-1,3,5-triazin-2(1H)-one
JSmol)
  • O=C1/N=C(\N=C/N1[C@@H]2O[C@@H]([C@@H](O)C2)CO)N
  • InChI=1S/C8H12N4O4/c9-7-10-3-12(8(15)11-7)6-1-4(14)5(2-13)16-6/h3-6,13-14H,1-2H2,(H2,9,11,15)/t4-,5+,6+/m0/s1 checkY
  • Key:XAUDJQYHKZQPEU-KVQBGUIXSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Decitabine (i.e., 5-aza-2′-deoxycytidine), sold under the brand name Dacogen among others, acts as a nucleic acid synthesis inhibitor.

analog
.

Medical uses

Decitabine is used to treat

refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia) and Intermediate-1, Intermediate-2, and High-Risk International Prognostic Scoring System groups. In patients with chronic kidney disease, Batty and colleagues reported the first case series on the feasibility of therapy with hypomethylating agents in patients with chronic kidney disease.[5]

It also has EU approval for acute myeloid leukemia (AML).[4]

Pharmacology

Decitabine is a hypomethylating agent.[6][7] It hypomethylates DNA by inhibiting DNA methyltransferase.

It functions in a similar manner to azacitidine, although decitabine can only be incorporated into DNA strands while azacitidine can be incorporated into both DNA and RNA chains.

It incorporates into DNA strands upon replication, and then when DNA methyltransferases (DNMTs) such as DNMT1, are engaged to bind the DNA and to replicate the methylation to the daughter strand, DNMTs are bound to decitabine irreversibly and cannot disengage. Therefore, the action of decitabine is division-dependent, meaning the cells have to divide in order for the pharmaceutical to act. Therefore, cancer cells which divide much more rapidly than most other cells in the body will be more severely affected by decitabine just because they replicate more. It seems that DNA hypermethylation is critical for development of cancer cells, and specifically for haematological malignancies. Methylation of CpG islands upstream of tumor suppressor genes in order to silence them seems to be critical for these type of cancers. Thus at optimal doses, decitabine blocks this type of methylation and has an anti-neoplastic effect.

Research

Atherosclerosis

A number of investigators have shown a relationship between

macrophages.[8]

References

  1. ^ "Summary Basis of Decision (SBD) for Dacogen". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  2. ^ "Summary Basis of Decision (SBD) for Demylocan". Health Canada. 23 October 2014. Retrieved 29 May 2022.
  3. ^ "Decitabine". National Center for Biotechnology Information. Retrieved September 24, 2016.
  4. ^ a b "EC Approves Marketing Authorization Of DACOGEN For Acute Myeloid Leukemia". 2012-09-28. Retrieved 28 September 2012.
  5. PMID 20511166
    .
  6. S2CID 9556660
    .
  7. S2CID 1149318
    .
  8. PMID 25953647
    .

Further reading

External links

  • "Decitabine". Drug Information Portal. U.S. National Library of Medicine.
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