Discussion

SUMO is a ubiquitin-like protein which is covalently linked to a large number of proteins controlling their function and localisation, in a process termed SUMOylation. SUMOylation is a dynamic event that in humans is reversed by Sentrin/SUMO-specific proteases (SENPs). There are nine SENPs in humans, which can be divided into three distinct classes based on their structure. SENPs display differential specificity towards the three SUMO isoforms (SUMO1, SUMO2, SUMO3) and are involved in two distinct activities: the maturation of SUMO precursors (endopeptidase activity) and/or SUMO deconjugation from substrates (isopeptidase activity). Notably, SENPs have been implicated in the pathogenesis of several human diseases, including cancer and neurodegenerative disorders making them attractive targets for drug discovery.
MISSION Therapeutics is a leading expert in DUB drug discovery, with a number of projects in lead optimisation. As part of ongoing efforts to expand its platform, MISSION has started validating SENPs as interesting targets in oncology and to develop SENP inhibitors. Targeting SENPs for drug discovery poses distinct challenges, including the characterization of SENP enzymatic activity and substrate specificity, and the development of high throughput primary and secondary biochemical assays, as well as cellular assays. MISSION has successfully developed a screening platform for SENPs which is currently being utilised to screen its proprietary DUB-focused compound library to identify drug-like starting points for SENP inhibition.