Biochemical Society Transactions | Year: 2010
Proteases play a key role in various pathological processes and several protease inhibitors are already available for treatment. DUBs (deubiquitinating enzymes) constitute one of the largest classes of human proteases and are key effectors of the ubiquitin-proteasome system. This pathway regulating cellular protein turnover has been implicated in the pathogenesis of many human diseases, including neurodegenerative disorders, viral diseases and cancer. The therapeutic efficacy of the proteasome inhibitor Velcader (bortezomib) for treating multiple myeloma and mantle cell lymphoma establishes this system as a valid target for cancer treatment. A promising alternative to targeting the proteasome itself would be to target the upstream, ubiquitin conjugation/deconjugation system, to generate more specific, less toxic anticancer agents. Advances in small molecule-based inhibitors specifically targeting DUBs are presented in this review. © The Authors Journal compilation.
Legrain P.,Ecole Polytechnique - Palaiseau |
Journal of Proteomics | Year: 2014
Intensive methodological developments and technology innovation have been devoted to protein-protein interaction studies over 20. years. Genetic indirect assays and sophisticated large scale biochemical analyses have jointly contributed to the elucidation of protein-protein interactions, still with a lot of drawbacks despite heavy investment in human resources and technologies. With the most recent developments in mass spectrometry and computational tools for studying protein content of complex samples, the initial goal of deciphering molecular bases of biological functions is now within reach. Here, we described the various steps of this process and gave examples of key milestones in this scientific story line.This article is part of a Special Issue entitled: 20. years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez. © 2014 Elsevier B.V.
Hybrigenics | Date: 2011-01-17
The present invention concerns the discovery of new selective inhibitors of ubiquitin specific proteases, their process of preparation and their therapeutic use.
Hybrigenics | Date: 2012-08-29
The present invention relates to quinazolin-4-one compounds of formula (I), their process of preparation and uses thereof. These compounds are useful as selective and reversible inhibitors of ubiquitin specific proteases, particularly USP7, for treating e.g. cancer, neurodegenerative diseases, inflammatory disorders and viral infections.
Hybrigenics | Date: 2011-07-13
The present invention provides new formulations of 14-epi-analogues of vitamin D, such as inecalcitol, providing improved absorption profile.