Parkinson’s disease: Servier and Oncodesign announce the selection of a preclinical candidate
Initiated in March 2019, this Research and Development partnership is focused on the identification of LRRK2 kinase inhibitors derived from Oncodesign’s proprietary Nanocyclix® platform and their potential to act as therapeutic agents against Parkinson’s disease, drawing on Servier and Oncodesign’s complementary expertise in the field of neurodegenerative disease and kinase inhibitors.
Why is probe-based drug discovery the key to leveraging innovation?
Oncodesign has developed a unique approach to drug discovery using probes which is highly complementary to the more traditional target-based approach. We have shown that this approach can generate exceptional drug candidates and bring new hope to patients with cancer, inflammatory and autoimmune diseases as well as central nervous system diseases.
Our process is based on the diversified chemistry of Nanocyclix®, which provides high-quality probes, i.e. potent macrocyclic kinase inhibitors with initial selectivity against a small “signature subset” of kinases.
Preliminary SAR demonstrated with minimal number of molecules
L’approche Probe-based de Nanocyclix®
Extensive profiling of the human kinome and early ADME testing can identify probes of interest with initial potency and selectivity against a small number of kinases. For selected inhibitor/target pairs, extensive literature and patent research is performed during the probe qualification phase to establish hypotheses on their therapeutic benefit. In the next step of probe orientation, Nanocyclix® probes are used to validate these hypotheses in both mechanism-based and translational target engagement models.
Probe to lead and lead optimization rely on the intrinsic properties of Nanocyclix® inhibitors; we improve the parameters of the molecules to a predefined Targeted Profile Product (TPP) while maintaining initial potency and selectivity to select a preclinical candidate. The molecules undergo an exhaustive series of biological tests, while at the same time continuing their optimization cycles in medicinal chemistry.
During these early steps, molecules and programs are already available for co-development partnerships.
We also selected a diverse set of approximately 500 Nanocyclix® molecules from different chemical series. This set of inhibitors based on the human kinome is a unique asset for phenotype-based approaches, as it ensures potency, selectivity, cellular activity and novelty from the outset. The deconvolution of active hits is supported by our broad knowledge base and is initially entirely focused on kinome activity.