Epigenetic Probes for HMTs

DESCRIPTION provided by applicant Epigenetic proteins such as histone methyltransferases represent important potential drug targets for indications like cancers neurodegenerative disorders and cardiovascular and metabolic diseases At Reaction Biology Corporation andquot RBCandquot we are working toward the complete coverage of all epigenetic targets including HMTs to identify and improve epigenetic modulators that can be used in research and drug discovery In this Phase II application we have proposed three aims following successful Phase I studies to continue the understanding of HMTsandapos biological functions and as new drug targets The aims include Complete the screening of HMTs for identifying new probes and building the chemical epigenetic data base Broader HTS and Structure Activity Relationship SAR study to identify and increase the potency of NSD inhibitors and Evaluating NSD inhibitorsandapos efficacy in cell based assays and determining their kinetic MOAs and early DMPK tox profiles Weandapos ll meet the following milestones Develop and commercialize or more HMT probes as general research tools for at least HMTs Improve at least lead compoundsandapos potency into the nanomolar range against NSDs that have different structure scaffolds with good cell based activity and DMPK profiles and we will be able to launch one of the largest publicly available chemical epigenetic data bases built on the screening activities from the compound collections that include most of the FDA approved drugs clinical trial agents diversified libraries and natural products PUBLIC HEALTH RELEVANCE Epigenetic proteins such as histone methyltransferases represent important potential drug targets for indications like cancers neurodegenerative disorders and cardiovascular and metabolic diseases If medicine is to move beyond conventional drug targets that represent symptomatic treatment only then validation of these epigenetic enzymes and factors as drug targets remains a top priority for drug discovery Chemical epigenetic inhibitors represent a powerful opportunity here However histone methylation is a relatively new discovery space and the likely structures of HMT inhibitors are not well defined Few small molecule inhibitors are available either for laboratory research or fo lead development Therefore there is a significant and urgent need to develop assays and to identify new chemical probes for these targets Small molecule probes would serve a valuable role in scientific investigations and serve as medicinal chemistry scaffolds for lead development and drug discovery With the completion of this application we will be able to provide high quality probes that can be used to validate epigenetic targetsandapos biological activities as a standard reference to customersandapos drug development activities and as leads for potential therapeutic agents In addition we will be able to launch one of the largest publicly available chemical epigenetic data bases built on the screening activities from the compound collections that include most of the FDA approved drugs clinical trial agents diversified libraries and natural products