Ubiquitin is a small protein used by living cells to regulate the presence or the abundance of intracellular proteins. The cells “stick” ubiquitin “tags” on the proteins that they want to get rid of by sending them to the proteasome, their protein “grinder”. Deubiquitinating enzymes function as “recycling agents” by removing the ubiquitin “tags” from the proteins which are back to their native functional state.
In the case of oncoproteins (proteins involved in the onset or development of cancers), the role of DUBs is detrimental because they recycle oncoproteins indifferently from the other proteins. Inhibiting a DUB which is recycling an oncoprotein results in the forced degradation of this oncoprotein and, therefore, in the reduction of its oncogenic activity. This is the rationale behind Hybrigenics Pharma' research in the ubiquitin-proteasome pathway, upstream of the proteasome, and the basis for a potential new class of innovative anticancer drugs.
Having pioneered the identification and validation of DUBs as oncology targets, Hybrigenics Pharma has focused its drug discovery efforts on Ubiquitin-Specific Protease 7 (USP7) and Ubiquitin-Specific Protease 8 (USP8). USP7 is a nuclear DUB involved in the recycling of proteins responsible for the integrity of the genome, and USP8 is a cytoplasmic DUB involved in the recycling of membrane receptors.
Hybrigenics Pharma’s estate of granted patents is the widest of the published intellectual property in the field of USP inhibitors, protecting five chemical families and covering more than thirty countries. Hybrigenics Pharma' research know how and expertise range from target discovery and validation to drug candidate selection including:
• Advanced disease-relevant, cellular phenotypic assays and interference technologies,
• High Throughput Screening of protein interactions and intracellular pathway mapping,
• High Throughput Screening of chemical libraries in biochemical and cellular assays,
• Molecular modelling and 3D structural studies,
• Patented series of USP7 or USP8 inhibitors.