Enabling Epigenetics Studies from HTS to SAR : A Novel HTRF® Platform to Identify and Characterize Reader Domain Inhibitors
Poster Oct 10, 2014
T. Roux1, M. Badol1, N. Douayry1, L. Sergeant1, E.Trinquet1, F. Degorce1, S. Milhas2, S. Betzi2, C. Derviaux2, C. Eydoux3, J. Letienne2, A. Lugari2, Y. Collette2, J-C. Guillemot3 et X. Morelli2
Over recent years, significant drug discovery efforts have been made to identify potent and selective inhibitors of epigenetic targets. Proteins of this target class are classified into readers, writers and erasers of marks on histones or other nuclear proteins and DNA. By regulating a combination of posttranslational marks, they tightly control gene expression. Their deregulation has been linked to the development of various diseases, particularly in oncology.
Here we describe a novel assay platform based on the HTRF technology which enables the discovery and the characterization of novel reader domain inhibitors. More than 20 different assays have been built up to monitor the interaction of Bromodomain, Tudor domains, MBT domains and Chromodomains with histone peptides.
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We utilized paired synthetic crRNAs coupled with our synthetic tracrRNA in cells transduced with lentiviral Cas9 to perform a functional knockout on hsa-miR-221. This three-part system (crRNA, tracrRNA and Cas9) has demonstrated efficient gene editing when used with only one guide RNA, but the goal was to use two crRNAs to remove the entire stem-loop.READ MORE
A New Method for Analyzing MSe/All Ions Fragmentation in Xenobiotic Metabolism StudiesPoster
During early drug discovery, the study of metabolism plays an essential role in determining which drug candidates move forward into development and later stages. As an alternative to traditional Data Dependent Acquisition (DDA), the use of MSE/All Ions Fragmentation (AIF) has become common in metabolite identification workflows for the analysis of metabolic hot spots. Here we present a solution for analysis of MSE/AlF in metID studies.READ MORE
A Real-Time Annexin V Method for Monitoring Programmed Cell DeathPoster
The RealTime-Glo™ Annexin V Apoptosis and Necrosis Assay detects the kinetics of apoptosis and secondary necrosis in real time resulting from a variety of treatments (including biologics) to induce cell deathREAD MORE
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