Jumonji domain-containing protein D3 (JMJD3, KDM6B) Targeted Library

The JMJD3, also known as lysine-specific demethylase 6B (KDM6B), is a histone demethylase that regulates the trimethylation of histone H3 on lysine 27 (H3K27me3) which is an important epigenetic event associated with transcriptional silencing. JMJD3 has been widely studied in various immune diseases, cancer and tumor development. Moreover, JMJD3 is involved in a variety of cellular processes, such as proliferation, differentiation and apoptosis. There is a comprehensive epigenetic transformation during the transition of embryonic stem cells (ESCs) into specialized cells or the reprogramming of somatic cells to induced pluripotent stem cells (iPSCs). The regulation of JMJD3 is highly genetic and context specific, and it is involved in a variety of tissue responses such as vertebrate development, cancer, inflammation and neurodegenerative diseases.

Aiming to discover JMJD3s inhibitors, BOC Sciences has developed a high-quality jumonji domain-containing protein D3 targeted library to peroform screening projects in KDM-related drug discovery.

Figure 1. Jmjd3 upregulates Ink4a/Arf and p21 by modulating H3K4 and H3K27 methylation. (Wei, Zhao.; et al. 2013)

Library Design

BOC Sciences applies a docking-based high-throughput virtual screening strategy to construct this library:

1. A receptor-based virtual screening workflow is established based on X-ray data for the complexes with 3-[[2-Pyridin-2-Yl-6-(1,2,4,5-Tetrahydro-3-Benzazepin-3-Yl)pyrimidin-4-Yl]amino]propanoic acid derivatives using Schrödinger software
2. The binding ligands have been extracted from the JMJD3 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: 4ASK
4. The docking procedure implied constraining the two critical features contributing to the ligand-binding-ligand-metal (Zn²⁺) coordination
5. Finally, 1200 potential JMJD3s inhibitors selected with computational chemistry and virtual screening techniques are generated successfully

Jumonji domain-containing protein D3 (JMJD3, KDM6B) 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 Jumonji domain-containing protein D3 (JMJD3, KDM6B) Targeted Library design at competitive prices for global customers. Personalized and customized services of Jumonji domain-containing protein D3 (JMJD3, KDM6B) 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!