Decitabine

Biological Activity

Decitabine is a potent DNA methyltransferase inhibitor with IC50 of 438 nM and 4.38 nM in HL-60 and KG1a cells, respectively. Decitabine is a hypomethylating agent. It hypomethylates DNA by inhibiting DNA methyltransferase. The DNA methyltransferase inhibitor Decitabine is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic compound in several hematological malignancies. Decitabine exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. The combination of Decitabine with TSA or depsi produced a greater inhibition of growth and DNA synthesis and a greater loss of clonogenicity than either agent alone. Decitabine is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use. In clinical trials, Decitabine was demonstrated to be an active antileukemic agent.

Product Citations

• 

  Free Radic Biol Med. 2023 Feb 1;195:359-370.

  ROS induced the Rab26 promoter hypermethylation to promote cigarette smoking-induced airway epithelial inflammation of COPD through activation of MAPK
  Decitabine purchased from AbMole

• 

  Cell Biol Toxicol. 2022 Apr;38(2):291-310.

  Lnc-HZ08 regulates BPDE-induced trophoblast cell dysfunctions by promoting PI3K ubiquitin degradation and is associated with miscarriage
  Decitabine purchased from AbMole

• 

  Clin Epigenetics. 2021 Jul 22;13(1):142.

  Genome-wide DNA methylome analysis identifies methylation signatures associated with survival and drug resistance of ovarian cancers
  Decitabine purchased from AbMole

• 

  Nat Commun. 2019 Dec 20;10(1):5799.

  Novel approach reveals genomic landscapes of single-strand DNA breaks with nucleotide resolution in human cells.
  Decitabine purchased from AbMole

• 

  Cell Physiol Biochem. 2018;50(6):2341-2364.

  Peperomin E Induces Promoter Hypomethylation of Metastatic-Suppressor Genes and Attenuates Metastasis in Poorly Differentiated Gastric Cancer.
  Decitabine purchased from AbMole

Chemical Information

Molecular Weight	228.21
Formula	C8H12N4O4
CAS Number	2353-33-5
Solubility (25°C)	DMSO 30 mg/mL Water ≥10 mg/mL
Storage	-20°C, protect from light, sealed

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Hassler MR, et al. Biochimie. Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine in anaplastic large cell lymphoma.

[2] Kantarjian H, et al. Cancer. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study.

[3] Momparler RL. Semin Hematol. Pharmacology of 5-Aza-2'-deoxycytidine (decitabine).

[4] Kantarjian HM, et al. Cancer. Results of decitabine (5-aza-2'deoxycytidine) therapy in 130 patients with chronic myelogenous leukemia.