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Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.2.2-1 | Award Amount: 8.22M | Year: 2013

In spite of valuable approaches applied to get a broad understanding of genetic, epidemiologic and molecular and system-level biological principles of human aging, cognitive decline remains as one of the greatest health challenges of the old age, with nearly 50% of adults over 85 afflicted of Alzheimers disease. Furthermore, drug development has not performed as expected in clinical trials, at least in part because of an insufficient mechanistic understanding at the systemic level in human. AgedBrainSYSBIO is a timely and straightforward project based on the integration of available transcriptomics, proteomics and metabolomics data, addition of relevant novel sets of data, their modeling and experimental testing in both human, mouse and drosophila. The concept is to identify subsets of pathways with two unique druggable hallmarks: (i) the validation of interactions occurring locally in subregions of neurons and (ii) a human and/or primate accelerated evolutionary signature, using six interacting approaches: (1) the identification of interacting protein networks from recent Late-Onset Alzheimer Disease- Genome Wide Association Studies (LOAD-GWAS) data, (2) the experimental validation of interconnected networks working in subregion of a neuron (such as dendrites and dendritic spines), (3) the inclusion of these experimentally validated networks in larger networks obtained from available databases to extend possible protein interactions, (4) the identification of human and/or primate positive selection either in coding or in regulatory gene sequences,(5) the manipulation of these human and/or primate accelerated evolutionary interacting proteins in human neurons derived from induced Pluripotent Stem Cells (iPSCs) and modeling prediction challenged in drosophila and novel mouse transgenic models. This work will finally allow (6) the validation of new druggable targets and markers as a proof-of-concept towards the prevention and cure of aging cognitive defects.


Colland F.,Hybrigenics
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.


The present invention concerns the discovery of new selective inhibitors of ubiquitin specific proteases, their process of preparation and their therapeutic use.


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.


The present invention concerns a process of isomerizing trans fused bicyclic derivatives into cis fused bicyclic derivatives and the preparation of vitamin D or analogs thereof comprising said isomerisation step.


Patent
Hybrigenics | Date: 2012-01-18

The present invention provides new formulations of 14-epi-analogues of vitamin D, such as inecalcitol, providing improved absorption profile.


Patent
Hybrigenics | Date: 2012-01-18

The present invention provides new formulations of 14-epi-analogues of vitamin D, such as inecalcitol, providing improved absorption profile.


The present invention relates to compounds of formula (I)


The present invention concerns a process of isomerizing trans fused bicyclic derivatives into cis fused bicyclic derivatives and the preparation of vitamin D or analogs thereof comprising said isomerisation step.


Patent
Hybrigenics | Date: 2012-01-18

The present invention provides new formulations of 14-epi-analogues of vitamin D, such as inecalcitol, providing improved absorption profile.

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