Epigenetics refers to a broad range of heritable changes in gene expression that are not caused by alterations in the DNA sequence itself. In general, a epigenetic change precedes disease pathology, which make it a valuable diagnostic indicator for disease risk or prognostic indicators for disease progression. A diversity of types of epigenetic processes have been identified, including DNA methylation, alterations in histone structure and gene regulation via small non-coding microRNAs. Epigenetics therefore plays an important role in many types of diseases, including cardiovascular diseases, neurological disorders, metabolic disorders, cancer, and several others. Nowadays, epigenetics has become an important area in drug therapy due to the nature of reversibility of epigenetic events.
At BOC Sciences, our well-developed high-throughput (HTS) platform enables us to establish chemical libraries against specific epigenetic biochemical targets. The epigenetic screening library contains screening compounds with drug-like phenotypes that are carefully selected via computational chemistry and virtual screening techniques to facilitate epigenetic-target drug discovery.
Figure 1. Epigenetic drug library screening for compounds specifically promoting the differentiation of Utx-null HSPCs. (Bao, W.; et al. 2019)
Epigenetic Screening Library Design
BOC Sciences has developed two epigenetic screening libraries using ligand-based and structure-based approaches, respectively.
Epigenetic focused libraries via 2D fingerprint similarity search
- A reference set of known epigenetic modulator molecules is obtained from the ChEMBL database, which includes all available compounds with known high activity against human epigenetic targets
- Next, a 2D fingerprint similarity search is performed on the BOC Sciences HTS compound set. 2D fingerprint similarity means that the subset of reference active compounds and the molecule of interest are represented as a set of small fragments encoded in a bit string (fingerprint), and then the two sets of ‘fingerprints’ are compared to estimate their degree of similarity
- Finally, 3,500 epigenetics-related screening compounds are generated successfully
Epigenetic targeted library via docking screening
This library contains 8,000 structurally diverse screening molecules that are screened through virtual screening against the following epigenetic targets:
- Jumonji domain-containing protein D3 (JMJD3, KDM6B)
- Histone methyltransferase EZH2
- Polycomb protein EED
- Protein arginine N-methyltransferase 6 (PRMT6)
- Histone lysine N-methyltransferase EHMT2 (G9a)
- Poly[ADP-ribose] polymerase 1 (PARP-1)
- Lysine-specific demethylase 4A (KDM4A)
- Menin/MLL
Epigenetic Screening Library Characteristics
- No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
- Unique small molecule regulators with biological activity for epigenetic studies and related assays
- The library contains epigenetics-related compounds targeting HDAC, histone demethylases, histone acetyltransferases (HAT), DNA methyltransferases (DNMT), epigenetic reader domains, microRNAs, etc
- Valuable tool for epigenetic target identification in chemogenomics, pharmacogenomics and other biological applications
- 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 Epigenetic Screening Library design at competitive prices for global customers. Personalized and customized services of Epigenetic Screening 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!
Reference
- Bao, W.; et al. Epigenetic drug library screening identified an LSD1 inhibitor to target UTX-deficient cells for differentiation therapy. Signal Transduction & Targeted Therapy. 2019. 4: 11.
