Polycomb protein EED Targeted Library

The Polycomb Group (PcG) family of proteins is a class of extremely conserved transcriptional repressors that regulate numerous epigenetic regulators of important life events. PcG are thought to be highly relevant to the development of many cancers. Polycomb repressor complex 2 (PRC2) is a key component in the regulation of gene expression, and is involved in cell development and differentiation. Abnormal activity of PRC2 has been observed in the progression of many human cancers, and its higher activity leads to increased levels of H3K27me3, which has been associated with different types of cancers, including prostate, breast, lymphoma and myeloma cancers. The WD40 repeat-containing protein EED is a core component of PRC2 which enhances its activity by interacting with the H3K27me3. The PRC2/EED-EZH2 complex can serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Pharmacological interventions against this component of PRC2 have attracted a widespread attention, and scientists are focused on investigating and discovering novel EED inhibitors.

BOC Sciences has created a reliable polycomb protein EED targeted library to identify and screen polycomb protein EED inhibitors.

Figure 1. Degradation of polycomb repressive complex 2 with an EED-targeted bivalent chemical degrader. (Potjewyd, F.; et al. 2019)

Library Design

BOC Sciences has employed a docking-based high-throughput virtual screening approach to construct this library:

1. A receptor-based virtual screening processis established based on X-ray data for the complexes with a 2-[4-(4-{(3S,4R)-4-(dimethylamino)-1-[(2-fluoro-6-methylphenyl)methyl]pyrrolidin-3-yl}phenyl)-1H-pyrazol-1-yl]acetamide using Schrödinger software
2. The binding ligands have been extracted from the EED crystal structure
3. The compounds in the HTS compound collection have been pre-filtered using BOC Sciences' internal filters and then docked at the active site: 5U6D
4. The docking procedure implied constraining a critical features contributing to the hydrogen bond
5. Finally, a diversity of potential EDD inhibitors selected with computational chemistry and virtual screening techniques are generated successfully

Figure 2. Chemical structures of UNC6852 and UNC7043 containing an EED ligand. (Potjewyd, F.; et al. 2019)

Polycomb protein EED Targeted 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
• 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 Polycomb protein EED Targeted Library design at competitive prices for global customers. Personalized and customized services of Polycomb protein EED Targeted 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!