Bromodomains are epigenetic readers that bind to acetyl-lysine residues on histones and other nuclear proteins. The four commonly expressed bromodomain and extraterminal domain (BET) proteins (Brd2, Brd3, Brd4 and Brdt) have emerged as potential targets for the treatment of a wide range of diseases, including diabetes, cardiovascular disease and chronic kidney disease. BET proteins also recognize acetylated non-histone proteins, including different transcription factors. The epigenome is usually unregulated in cancer and treatment with inhibitors of bromodomain and extra-terminal proteins (readers of epigenetic acetylation markers), which represents a new therapeutic approach. Results from preclinical studies have demonstrated the role of BET proteins in human cancer and provided a rationale for targeting BET proteins as a strategy to develop new anti-cancer drugs. Genetic screening procedures performed for different tumor types have also identified the genes encoding BET proteins as those on which neoplastic cells depend. BET bromodomain inhibition could provide a new therapeutic approach for a number of diseases, including diabetes, cardiovascular and neurodegenerative diseases.
BOC Sciences is focused on establishing a BET bromodomain inhibitors library to explore novel bromodomain and BET inhibitor.
Figure 1. BET-Bromodomain Inhibitors Engage the Host Immune System. (Hogg, S. J.; et al. 2017)
Library Design
At BOC Sciences, our experts have established a high-throughput virtual screening method based on molecular docking approach to generate this library:
- A receptor-based virtual screening process is created based on X-ray data for the complexes: 4J1P
- The compounds in the HTS compound collection have been pre-filtered using BOC Sciences' internal filters and then docked at the active site. Moreover, a variety of H-bond constraints: HOH604, ASN429 are taken into consideration
- Finally, 1,573 potential bromodomain and BET inhibitors selected with computational chemistry and virtual screening techniques are generated successfully
Figure 2. Selective N-Terminal BET Bromodomain Inhibitors by Targeting Non-Conserved Residues and Structured Water Displacement. (Cui, H.; et al. 2021)
BET Bromodomain Inhibitors Library Characteristics
- No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
- Bioactivity and safety confirmed by preclinical studies and clinical trials
- Structural diversity, medicinal activity, and cellular penetration
- Structural document, IC50, and other chemical and biological data are provided
- All compounds are continually updated
- All of these compounds with Tanimoto index ≥ 0.85
- Compound cherry-picking service is provided
What We Deliver
- Delivered within 2 weeks in any customer-preferred format
- Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
- All compounds have a minimum purity of 90% assessed by 1H NMR and HPLC
- Analytical data is provided
BOC Sciences provides professional, rapid and high-quality services of BET Bromodomain Inhibitors Library design at competitive prices for global customers. Personalized and customized services of BET Bromodomain Inhibitors Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!
References
- Hogg, S. J.; et al. BET-Bromodomain Inhibitors Engage the Host Immune System and Regulate Expression of the Immune Checkpoint Ligand PD-L1. Cell Reports. 2017. 18(9): 2162-2174.
- Cui, H.; et al. Selective N‐Terminal BET Bromodomain Inhibitors by Targeting Non‐Conserved Residues and Structured Water Displacement. Angewandte Chemie. 2021. 60(3): 1220-1226.
