Functional Diversity of DNA Methyltransferase Inhibitors Functional Diversity of DNA Methyltransferase Inhibitors.

Abstract:
DNA methylation is catalysed by an enzyme called DNA methyltransferases. Human genome have four DNA methyltransferase genes,DNMT1, DNMT2, DNMT3A, and DNMT3B, still not resolved how these proteins been deregulated through cellular transformation. These proteins will have a big relief for people struggling with the tumours, the first one in the list (5-azacytidine, Vidaza) has been approved as an antitumor agent and the others are in their way of their preclinical and clinical development. They found the most common used DNA methyltransferase inhibitors, 5-azacytidine (5-aza-CR), it’s been characterised 25 years ago. 5-aza-CR need to be incorporated into DNA, this compound need to need extensive modification through metabolic pathways. In this study main focus on the cytosine analogue 5-aza-CR and 5-aza-CdR, both of them been wildly used in clinical trials and have been success to be effective in a variety of hematologic disorders. Generally the drugs been divided into two groups first one 5-aza-CR,5-aza-CdR, and zebularine, these been called nucleoside and the second group called non-nucleoside which contain procaine, EGCG, and RG108. Finally the most favoured drug currently used (5-aza-CdR)had the highest genotoxicity . In spit of cytotoxicity of azanucleoside inhibitors also showed the strongest demethylation effects . In addition to that we found 5-aza-CR and 5-aza-CdR the only drugs capable of significant demethylation and reactivation of the TIMP-3 tumor suppressor gene.

BIOC6006
Name: Ammar Alhassany
ID: 41874259