DNA methyltransferase 1 (DNMT1), one of the main epigenetic targets, is involved in the duplication of the DNA methylation pattern during replication, and it is essential for proper mammalian development. Small molecu...DNA methyltransferase 1 (DNMT1), one of the main epigenetic targets, is involved in the duplication of the DNA methylation pattern during replication, and it is essential for proper mammalian development. Small molecule DNMT1 modulators are attractive for biochemical epigenetic studies and have the potential to become drugs. So far, more than five hundred small molecules have been reported as DNMT1 inhibitors. However, only a limited number of DNMT1 activators have been disclosed because, at least in part, DNMT1 activators are typically regarded as negative data in virtual screening campaigns or optimization projects. This manuscript aims to report the chemical structures and biological activity of small molecules that increase the enzymatic activity of DNMT1. Results of the biochemical experimental assays are discussed. It was found that small molecule activators have a large variety of chemical scaffolds but share pharmacophore features. Visual analysis of the chemical space and multiverse based on molecular fingertips supported that activators are structurally diverse. This is the first report of eight small molecules that increase the enzymatic activity of DNMT1 by more than 400% in an enzymatic-based assay. The outcome warrants further investigation of the epigenetic activity of the compounds in a counter-screen assay, e.g., cell-based and in vivo context.展开更多
Scheduled for vol. 51 issue 8, August 2008 Chemoinformatics and chemometrics are the use of informatics methodology to investigate chemical problems, existing at the interface between chemistry, biology, material scie...Scheduled for vol. 51 issue 8, August 2008 Chemoinformatics and chemometrics are the use of informatics methodology to investigate chemical problems, existing at the interface between chemistry, biology, material science and computer science. Through their devel-opment during展开更多
Chemoinformatics is the application of informatics methods to solve chemical problems. Although this term was introduced only a few years ago, this field has a long history with its roots going back more than 40 years...Chemoinformatics is the application of informatics methods to solve chemical problems. Although this term was introduced only a few years ago, this field has a long history with its roots going back more than 40 years. These different origins have now merged into a discipline of its own that is full of activities. All areas of chemistry from analytical chemistry to drug design can benefit from chemoinformatics methods. And there are still many challenging chemical problems waiting for solutions through the further development of chemoinformatics.展开更多
文摘DNA methyltransferase 1 (DNMT1), one of the main epigenetic targets, is involved in the duplication of the DNA methylation pattern during replication, and it is essential for proper mammalian development. Small molecule DNMT1 modulators are attractive for biochemical epigenetic studies and have the potential to become drugs. So far, more than five hundred small molecules have been reported as DNMT1 inhibitors. However, only a limited number of DNMT1 activators have been disclosed because, at least in part, DNMT1 activators are typically regarded as negative data in virtual screening campaigns or optimization projects. This manuscript aims to report the chemical structures and biological activity of small molecules that increase the enzymatic activity of DNMT1. Results of the biochemical experimental assays are discussed. It was found that small molecule activators have a large variety of chemical scaffolds but share pharmacophore features. Visual analysis of the chemical space and multiverse based on molecular fingertips supported that activators are structurally diverse. This is the first report of eight small molecules that increase the enzymatic activity of DNMT1 by more than 400% in an enzymatic-based assay. The outcome warrants further investigation of the epigenetic activity of the compounds in a counter-screen assay, e.g., cell-based and in vivo context.
文摘Scheduled for vol. 51 issue 8, August 2008 Chemoinformatics and chemometrics are the use of informatics methodology to investigate chemical problems, existing at the interface between chemistry, biology, material science and computer science. Through their devel-opment during
文摘Chemoinformatics is the application of informatics methods to solve chemical problems. Although this term was introduced only a few years ago, this field has a long history with its roots going back more than 40 years. These different origins have now merged into a discipline of its own that is full of activities. All areas of chemistry from analytical chemistry to drug design can benefit from chemoinformatics methods. And there are still many challenging chemical problems waiting for solutions through the further development of chemoinformatics.
