Product Development for Bromodomain Networks

Product Development for Bromodomain NetworksAbstractEpigenetic regulation of gene expression is a highly dynamic and reversible process essential to normal cellular functionHoweverit also contributes to human diseasessuch as cancer and inflammationProtein families that participate in epigenetic regulation include writerswhich covalently modify chromatinreaderswhich recognize chromatin modificationsand eraserswhich remove modificationsA large volume of research in the field over the past decade has shown that many epigenetic proteins are potential druggable targetsBromodomainswhich belong to the readers categoryrecognize acetylated lysine residues on histones and other proteinsSeveral potentselective and cellularly active bromodomain compounds have recently been identifiedincreasing appreciation of the functional importance and therapeutic potential of this familyHoweverstudies are limited and focus only on a few bromodomain subfamiliessuch as the bromodomain and extraterminalBETproteinsThere are a number of reasons that the studies have not expanded into more reader proteinsthe key limitations are in both the availabilities of products and the body of knowledge for these non BET subfamily targetsAs part of the proposed Phase II application we ll concentrate onmajor worksto complete the screening of Bromodomains against the FDA approved drugs and NIH s clinical trial agent collections for identifying new probes and building the chemical epigenetic data baseto expand the HTS efforts to includetonew BRDs as potential drug targetsThese bromodomains will be good potential drug targetsbut have no probes or lack of good probes based on public domain informationandto develop potent and selective probes by SAR studies and evaluate their activities in cell based assaysThe lead compounds with unique scaffolds will be further tested with DMPK Tox assays as potential therapeutic agents