DNA methyltransferase inhibitors

Stresemann, C., Brueckner, B., Musch, T., Stopper, H. and Lyko, F. (2006) Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines. Cancer Research, 66, 2794—2800. 

Hydralazine is a vasodilating drug and inhibition of DNA methyltransferases in the range of 10-20 pM have been reported in vitro [83]. In addition, hypomethylation in cell culture has also been shovm [84]. Also the local anesthetic procaine [85] and its amide analog procainamide [84] have been identified as DNA methyltransferase inhibitors. Synthetic analogs of procaine have shown activity only around 500 pM [86] (Figure 8.10). 

Brueckner, B., Kuck, D. and Lyko, F. (2007) DNA methyltransferase inhibitors for cancer therapy. Cancer Journal (Sudbury, Mass), 13, 17-22. 

Stresemarm, C. and Lyko, F. (2008) Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine. International Journal of Cancer, 123, 8-13. 

Zhu, W.G. and Otterson, G.A. (2003) The interaction of histone deacetylase inhibitors and DNA methyltransferase inhibitors in the treatment of human cancer cells. Current Medicinal Chemistry Anticancer Agents, 3, 187-199. 

F (1997) is a potent histone deacetylase inhibitor, and psammaplin G (1998) is a potent DNA methyltransferase inhibitor. A Southern Japanese version of Pseudoceratina purpurea has yielded pseudoceratins A (2002) and B (2003) (1834). 

Figure 2 (A) DNA methyltransferase inhibitors. (B) Representative histone deacety-lase inhibitors. Source From Journal of the National Cancer Institute (89) copyright Oxford University Press, 2003.

DNA methyltransferase inhibitors represent promising new drugs for cancer therapies. Approval of the hypomethylating compounds 1 and 2 marked a recent,... 

Quddus J, Johnson KJ, Gavalchin J, Amento EP, Chrisp CE, Yung RL, Richardson BC (1993) Treating activated CD4+ T cell with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause lupus-like disease in syngeneic mice. J Clin Invest, 92(1) 38-53. 

Tan W, Zhou W, Yu HG, Luo HS, Shen L. The DNA methyltransferase inhibitor zebularine induces mitochondria-mediated apoptosis in gastric cancer cells in vitro and in vivo. Biochem Biophys Res Commun. 2013 4430 250-6. 

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