Inhibitor SourceBook™ Second Edition

DNA Methyltransferase Inhibitors
DNA methylation is one of the most prevalent epigenetic
modifications of DNA in mammalian genomes. It is
achieved by DNA methyltransferases that catalyze
the addition of a methyl group from S-adenosyl-
L-methionine to the 5-carbon position of cytosine.
Methylation at cytosine plays an important role in
regulating transcription and chromatin structure.
Methylated DNA can trigger chromatin reorganization
mediated by methyl-binding proteins. Four families
of DNA methyltransferase genes have been identified
in humans. They include Dnmt1, Dnmt2, and Dnmt3b,
which encode proteins with different functional
specificities. Dnmt1 is constitutively expressed in
proliferating cells and its inactivation results in
demethylation of genomic DNA and embryonic death.
Dnmt2 is expressed at low levels in adult tissues.
Its inactivation does not affect DNA methylation or
maintenance of methylation. Dnmt3a and Dnmt3b are
strongly expressed in embryonic stem cells, but are
down-regulated in differentiating embryonic stem cells
and in adult somatic cells.
Most mammalian transcription factors bind GC-rich DNA
elements, and methylation within these elements reduces
their ability to bind. CpG methylation is shown to induce
histone deacetylation, chromatin remodeling, and gene
silencing through a transcription repressor complex.
DNA Methyltransferase Inhibitors
Calbiochem • Inhibitor SourceBook
Cell Division/Cell Cycle/Cell Adhesion
CpG islands are often located around the promoters of
housekeeping genes and are not methylated. On the
contrary, the CG sequences in inactive genes are usually
methylated to suppress their expression.
Aberrant DNA methylation has been linked to several
pathological conditions. Mutations in DNA methyltransferase
3b are known to cause ICF (immunodeficiency,
centromere instability and facial anomalies) syndrome.
Overexpression of DNA methyltransferases has been
implicated in the development of several tumors. About
25% of all mutations in the p53 gene in human cancers
are reported to occur at CpG sites. Methylation of these
sites can inactivate and silence tumor suppressor genes.
Abnormal DNA methylation also occurs during aging and
alters gene activity, thus affecting a variety of cellular
functions.
References:
Stresemann, C. et al. 2006. Cancer Res. 66, 2794.
Lee, W.J. et al. 2005. Mol. Pharmacol. 68, 0 8.
Lyko, F., and Brown R. 2005. J. Natl. Cancer Inst. 97, 498.
Lehmann, U., et al. 2004. Ann. Hematol. 83, 37.
Paz, M.F., et al. 2003. Human Mol. Genetics 12, 2209.
Robertson, K.D. 200 . Oncogene 20, 3 39.
Xu, G.L., et al. 999. Nature 402, 87.
Okano, M., et al. 998. Nucleic Acids Res. 28, 2536.
Issa, J.P., et al. 993. J. Natl. Cancer Inst. 85, 235.
Product Cat. No. Comments Size Price
5-Aza-2´-Deoxycytidine 189825 (5-Aza-CdR; 5-Aza-dC; 5-Deoxy-2´-azacytidine)
A cytosine analog that acts as a DNA methyltransferase inhibitor. Also enhances
apoptosis induced by histone deacetylase inhibitors.
N DNA Methyltransferase
Inhibitor
(–)-Epigallocatechin
Gallate
More online... www.calbiochem.com/inhibitors/DNAm
260920 2-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-3-(1H-indol-3-yl)propionic acid; RG108
A cell-permeable specific inhibitor of DNA methyltransferases (IC 50 = 5 nM for
CpG methylase M.SssI) and displays anti-proliferative properties. Suggested to
directly target the enzyme active sites, block DNA methylation, and re-activate
tumor suppressor genes.
324880 A polyphenolic compound with antitumor, anti-inflammatory, and anti-oxidant
properties. An inhibitor of Dnmt1 (IC 50 = 2 0-470 nM).
N InSolution Sinefungin 567051 (A9145; Adenosyl-ornithine; SF)
A 0 mM (2 mg/524 ml) solution of Sinefungin in H 2 O. An anti-leishmanial
nucleoside antibiotic that acts as an S-adenosyl-L-methionine (SAM, AdoMet)
methyltransferase-specific inhibitor.
Zebularine 691400 [2-Pyrimidone-1-b-D-riboside; 1-(b-D-Ribofuranosyl)-1,2-dihydropyrimidin-2-one]
A chemically stable cytidine analog that displays antitumor properties. An inhibitor
of DNA methylation and tumor growth both in vitro and in vivo. Also acts as
transition state analog inhibitor of cytidine deaminase by binding at the active site
as covalent hydrates.
25 mg $ 78
0 mg $ 24
0 mg $39
2 mg $ 39
0 mg
25 mg
$ 2
$258
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