DNA Methyltransferase Inhibitor Discovery Services

DNA methylation, catalyzed by DNA methyltransferases (DNMTs), involves the addition of a methyl group to cytosine bases, primarily within CpG dinucleotides. Age-related changes in DNA methylation, including global hypomethylation and locus-specific hypermethylation, contribute to genomic instability, altered gene expression, and impaired cellular function. DNMT inhibitors, by interfering with the enzymatic activity of DNMTs, can restore or modulate these aberrant methylation patterns, potentially reversing or mitigating the effects of aging.

Fig. 1 Schematic representation of the changes in the methylome during aging. (Johnson AA, et al., 2012)

CD BioSciences provides comprehensive DNMT inhibitor discovery services. Our experts employ advanced technologies and expertise to identify and optimize novel inhibitors that target DNA methylation associated with aging.

How Do We Help Clients Develop DNA Methyltransferase Inhibitors?

Design and synthesis of DNA methyltransferase inhibitors

CD BioSciences leverages advanced computational tools and medicinal chemistry expertise to design and synthesize novel DNMT inhibitors with anti-agign effects. Based on structure-based drug design, we guide the rational design of molecules targeting specific DNMT isoforms, enhancing selectivity and minimizing off-target effects. We integrate molecular modeling, docking simulations, and pharmacophore mapping to identify potential inhibitors with optimal binding affinity and desirable physicochemical properties. Our iterative design, synthesis, and evaluation process leads to inhibitor optimization, improving potency and selectivity.

Assays for evaluating inhibitory activity

CD BioSciences employs a range of assays to evaluate the activity of DNA methyltransferase inhibitors. We use purified enzymes and cell-based reporter assays to measure the effect on DNMT-regulated gene expression. Our experts employ various detection techniques, including fluorescence-based assays and high-performance liquid chromatography (HPLC), to quantify DNMT inhibition. Our assays are validated using established positive and negative controls to ensure reliability and reproducibility. We also assess the effects of potential inhibitors on different DNMT isoforms to determine the selectivity of inhibition.

Binding mode studies

Understanding how DNMTs interact with their target enzymes is essential for optimizing their design. We utilize X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and molecular dynamics to elucidate the binding modes of DNMT inhibitors.

Epigenomic profiling

We use next-generation sequencing to analyze genome-wide DNA methylation patterns. Our services allow clients to identify specific methylation sites targeted by the inhibitors and determine their impact on gene expression.

Analysis of the Role of DNA Methyltransferase Inhibitors in Regulating Lifespan

CD BioSciences conducts extensive analyses to unravel the impact of DNMT inhibitors on lifespan regulation. We utilize established animal models (e.g., Caenorhabditis elegans, Drosophila, mice) to assess the effects of DNMT inhibitors on lifespan and healthspan. Our services also help clients measure various age-related parameters, including survival curves, locomotor activity, and age-related pathology.

At CD BioSciences, our comprehensive approach, encompassing design, synthesis, and rigorous testing, makes us a reliable service provider in developing DNMT inhibitors. Our commitment to excellence in research and development ensures that we remain a trusted partner in the quest for effective anti-aging therapeutics. If you are interested in our services, please feel free to contact us or make an online inquiry.

References

1. Johnson AA, et al. The role of DNA methylation in aging, rejuvenation, and age-related disease. Rejuvenation Res, 2012, 15 (5): 483-94.
2. Suzuki T, et al. Design, synthesis, inhibitory activity, and binding mode study of novel DNA methyltransferase 1 inhibitors. Bioorg Med Chem Lett, 2010, 20 (3): 1124-7.