Chromodomain Inhibitor Screening

1. Chromodomain Inhibitor Screening

2. Epigenetic posttranslational modifications (PTMs) of histone are critical for the regulation of eukaryotic transcription. Enzymes establishing and maintaining the epigenetic code are called “writer” and “eraser” by creating or removing posttranslational marks, respectively. Readers are specific binding proteins that recognize histone PTMs and mediate epigenetic signaling. The structure of reader domains provides a typical cavity or surface groove that can accommodate a specific epigenetic mark. Interactions between reader domain and the flanking sequence of the modified amino acid allow the protein containing reader domain to distinguish similar epigenetic marks, such as histone lysine mono-, di- and trimethylation. There are several reader domains associated with histone PTM recognition have been profoundly characterized, including bromodomain, chromodomain, multiple domain, malignant brain tumor (MBT), plant homeodomain (PHD), SET- and RING-associated domain (SRA) as well as Tudor domain. The bromodomain could target acetylated histones and regulate transcription, DNA repair, DNA replication and chromosome condensation. Chromodomain targets methylated lysine on H3, leading to either activation or silencing of gene expression. MBT domain binds with mono- and di- methylated lysine on H3 and H4 tails to regulate transcription. PHD domain causes gene activation by binding to methylated H3 and. DNA repair is mediated by Tudor domain that binds to methylated lysine at position 20 on H4, whereas its binding with methylated lysine at position 4 on H3 leads to transcription.

4. Given the physiological importance of epigenetic reader domains in gene transcription, pharmacological manipulation of these proteins may represent a promising new area for drug discovery against a broad array of disease states. The discovery of selective inhibitors targeting epigenetic readers has tremendously promoted the understanding of the epigenetic regulatory mechanisms as well as the molecular and structural determinants of binding specificity and druggability of these reader domains. To help make reader domain research possible, Creative BioMart offers a broad panel of reader domain assays. A versatile assay platform is utilized for the screening of small-molecule inhibitors and the detailed characterization of inhibitors. Our collection of reader domain assays can be used for screening, lead optimization or selectivity profiling to identify reader domain inhibitors. Our proficient experts will participate in every step of the process to provide high-quality solutions to make discovery possible. Along with this procedure, novel inhibitors of epigenetic reader domains are expected to drive early stage drug discovery for the targeted disease. Purified reader domains and inhibitor screening assay kits are also provided for purchase and assay service.

5. Creative BioMart assist our clients’ specific objectives in epigenetic drug development through a comprehensive set of screening services covering almost all proteins containing reader domain. Our Ph.D. level research group is also confident in tailoring service to achieve your goals in a high-quality, reliable and cost-effective manner. Please search our website for a full listing of available reader domain proteins, or alternatively request further information and price by contacting us.

6. Thank you ! Excerpt from: https://www.creativebiomart.net/epigenetics/services/epigenetic-drug-discovery/biochemical-assays/reader-domain-screening/