Identification and development of a small molecule probe for GNMT

National Center For Advancing Translational Sciences

Investigators

Abstract

The project team developed a unique primary assay for the methyltransferases (MTase) NNMT, PNMT, COMT, HNMT, GNMT, and GAMT, and also developed a counter-assay using a commercial luminescent methyltransferase kit. To date, the team has screened over 12,000 compounds from a number of small molecule libraries to begin building the activity profiles for each MTase. Virtual docking simulations and protein structure comparison efforts were launched to inform hypotheses about compounds which are pan inhibitors of the MTases, and which are selective to individual MTases. Current work is focused on high-throughput screening and subsequent medicinal chemistry to identify and characterize GNMT-specific inhibitors as chemical probes.