[Webinar] How to better optimize an oncology drug discovery program
Register for this webinar discussing how conventional and innovative integrated technological skills should be incorporated into an oncology program.Read more
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. It thus brings 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.
|Nanocyclix® Probe Criteria|
|Attractive PhysChem Properties: MW < 400, 2 < cLogP < 4, LE > 0.3, TPSA < 120A|
|Potent in binding/biochemistry assays: Kd/IC50 < 50nM|
|Selective against kinome: S50 @0.1µM < 5% / @1µM < 10%|
|Kinase signature identified|
|Identified therapeutic indication|
|In vitro target engagement or functional activity demonstrated|
|ADME characteristics demonstrating drug-like potential|
|Preliminary SAR demonstrated with minimal number of molecules|
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 created a diversity set of approximately 500 Nanocyclix® molecules from different chemical series. This set of inhibitors, profiled against 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.