Proteases play a key role in a number of pathological processes and several protease inhibitors are already available as drugs (ACE, HIV-1 proteases inhibitors,…) . Ubiquitin-specific proteases (USP), one of largest classes of human proteases, are key effectors of the ubiquitin-proteasome system. This pathway that regulates cellular protein turnover is implicated in the pathogenesis of a number of human diseases, including cancer. The only approved ubiquitin-proteasome system related therapeutic, Velcade®, has demonstrated proof of concept for proteasome inhibition in cancer. It shows, however, multiple undesirable side effects due to its broad ranging effects on protein degradation. A promising alternative to targeting the proteasome is to interact at the upstream level of ubiquitin conjugation/deconjugation to generate therapeutics with increased specificity and selectivity. Among the upstream ubiquitin transfer system, USP constitute one of the most favourable target classes due to their protease function being amenable to small molecule drug discovery and their previous successful exploitation by the pharmaceutical industry.

Hybrigenics is a leader in investigating ubiquitin-specific proteases for the discovery and development of new cancer therapeutics. The company has initiated a pioneering effort on the identification and validation of ubiquitin-specific protease targets in oncology. Hybrigenics has discovered innovative small molecule inhibitors of ubiquitin specific proteases showing potent anti-tumour activity in vivo. The company has built a unique platform in the molecular cell biology, enzymology and pharmacology of ubiquitin-specific proteases, and a patent portfolio covering advanced screening assays and original small molecule inhibitors.