Advancing Drug Discovery in an Academic Setting

Julie Frearson, Professor Biotechnology/Drug Discovery/Biological Chemistry and Molecular Pharmacology, University of Dundee

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Launch presentation

About the speaker

Following 8 years of signal transduction research at Kings College London (PhD) and The Babraham Institute in Cambridge, Julie joined a new start-up biotech focused on assay development and hit discovery for partners- Cambridge Drug Discovery. Throughout the period of the next 7 years she held numerous posts within this organization and latterly BioFocus plc, becoming Director of Biology when she assumed the Scientific and Commercial Leadership of the Biology Business. Her expertise covers target assessment, assay development, medium-high throughput screening and working with medicinal chemistry teams to deliver lead optimisation candidates. She also has experience and insight into the management and commercial realities of running a drug discovery business.
Professor Frearson now plays a key role in Drug Discovery at Dundee, focusing on accelerating the translation of basic life sciences research into therapeutic application in a number of areas including tropical neglected disease, cancer and stem cell applications.

Abstract

Protein kinase CK2 is a heterotetrameric serine/threonine kinase with a broad and acidophilic substrate profile. The CK2 holoenzyme is composed of two separate catalytic subunits (CK2?) attached to a dimer of non-catalytic chains (CK2?). CK2 activity is ubiquitously present in eukaryotic cells but significantly overexpressed in rapidly proliferating tissues, especially in tumor cells. Therefore, the enzyme is subject of pharmaceutical drug design efforts. So far these activities follow the classical strategy to target the canonical ATP-binding site of active protein kinases (type I inhibitors). The principal problem of this approach is that all members of the protein kinase superfamily are structurally similar in this region so that selectivity of an inhibitor is difficult to achieve. Novel structural results, however, suggest two alternative concepts: (1) type II inhibitors stabilize inactive kinase conformations which were so far unknown for CK2? but which have been found recently; (2) type III inhibitors bind to allosteric binding sites on the enzyme surface; in the case of CK2? the first molecules of this type have been identified. Some of them are weak CK2? antagonist and may be helpful to develop small molecules to address and disrupt the CK2?/CK2? interaction.

Launch presentation