Molecular modeling studies of the novel inhibitors of DNA methyltransferases SGI-1027 and CBC12: implications for the mechanism of inhibition of DNMTs.

ABSTRACT: DNA methylation is an epigenetic modification that regulates gene expression by DNA methyltransferases (DNMTs). Inhibition of DNMTs is a promising approach for cancer therapy. Recently, novel classes of the quinolone-based compound, SGI-1027, and RG108-procainamide conjugates, CBC12, have been identified as potent DNMT inhibitors. In this work, we report comprehensive studies using induced-fit docking of SGI-1027 and CBC12 with human DNMT1 and DNMT3A. The docking was performed in the C-terminal MTase catalytic domain, which contains the substrate and cofactor binding sites, in the presence and absence of other domains. Induced-fit docking predicts possible binding modes of the ligands through the appropriate structural changes in the receptor. This work suggests a hypothesis of the inhibit

SUBMITTER: Yoo J 

PROVIDER: S-EPMC3636198 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature