Lysine-specific demethylase 4A (KDM4A) Targeted Library

Histone methylation is an important epigenetic modification, and methylation is critical in many processes involved in cell differentiation, homeostasis and disease, occurring primarily at arginine/lysine residues and is mediated by numerous enzymes that share a common domain. To date, more than 20 human histone N-methylated lysine residue demethylases (KDM) have been identified of which KDM4A (also known as JMJD2A) specifically catalyzes the demethylation of lysine residues of histone proteins, thereby regulating chromatin structure and gene transcription. Recent studies have revealed that KDM4A is involved in the regulation of cell proliferation, differentiation, development, metabolism and other important biological processes, and its dysregulation function is also closely related to the development of tumors and other diseases, making it an important target for future tumor therapy. Therefore, the discovery of KDM4s inhibitors is a potential therapeutic strategy for various diseases, including cancer.

Aiming to discover KDM4s inhibitors as antitumor agents, BOC Sciences has developed a high quality lysine-specific demethylase 4A targeted library to carry out screening projects in KDM-related drug discovery.

Figure 1.Schematic representation of KDM4A-dependent degradation. (Johmura, Y.; Nakanishi, M. 2016)

Library Design

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

1. A receptor-based virtual screening workflow is established based on X-ray data for the complexes with a pyrido [3,4-d] pyrimidin-4(3H)-one derivatives using Schrödinger software
2. The binding ligands have been extracted from the KDM4A 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
4. The docking procedure implied constraining the two critical features contributing to the ligand-binding-ligand-metal (Zn2+) coordination and the presence of a ligand’s hydrophobic moiety between side chains of Ty177 and Phe185
5. Finally, 2,000 potential KDM4A inhibitors selected with computational chemistry and virtual screening techniques are generated successfully

Lysine-specific demethylase 4A (KDM4A) 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
• 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 Lysine-specific demethylase 4A (KDM4A) Targeted Library design at competitive prices for global customers. Personalized and customized services of Lysine-specific demethylase 4A (KDM4A) 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!