Nanocyclix® technology, a new generation of kinase inhibitors

There are three major challenges when it comes to inhibiting kinases:

Kinases play a key role in regulating most cellular functions, such as proliferation, the cell cycle, metabolism, survival/apoptosis, DNA repair, motility, and microenvironment response. Targeting kinases – a family of more than 500 proteins in the human genome that regulate cell signaling by transferring an ATP phosphate group to their substrate protein – represents a major opportunity in more than 400 diseases.

1.

Inhibitors need to be very potent to compete with high ATP levels in cells. The molecules that block the active site at the kinases must have on target nanomolar activities.

2.

Specificity is key. Inhibitors have to block only the kinase in question, without affecting the other 500+ kinases to avoid adverse effects.

3.

Compromising between the two challenges opposite tends to lead to molecules with physico-chemical properties that are less suitable for drug development. Inhibitors should be in what is called a “drug-like-space”.

Nanocyclix® is our first choice solution for these challenges. It is a new paradigm in of kinase inhibition. Since the 2000s, Nanocyclix® has been built and explored as a medicinal chemistry technology, a next generation kinase inhibitor platform and a new probe-based approach for drug discovery.

Discover Nanocyclix among our innovative technology platforms

The challenges ahead

  • POTENCY

    Need for low nM potency to compete with ATP levels in cells

  • SELECTIVITY

    Target one out of 518 kinases in the human kinome.

  • DRUG LIKE POTENTIAL
    • Low MW
    • Attractive physicochemical properties
    • Predictable SAR trends
    • BBB crossing if required
    • Tractable chemistry
    • Chemical scalability
    • Low human dosing
    • Acceptable safety profile
technology-nanocyclix-EN

Medicinal chemistry technology

Nanocyclix® technology increases the potency and specificity 1,000 fold for a “signature” of kinases

The principle of Nanocyclix® is simple: macrocyclization of the fragments that bind to the “hinge” region of kinase is used to generate potent and selective small molecules with low molecular weight and desirable physico-chemical properties. The cycle “linker” creates a rigid three-dimensional form specific to the molecule which is complementary to the ATP binding site at the kinases. The near-perfect fit between the binding site and the molecule explains both its potency and selectivity: calorimetric studies have shown that no entropic penalty should occur when the inhibitor binds to the site, unlike with linear compounds. This mechanism using shape recognition represents a new paradigm for type 1 kinase inhibitors and is widely used by Nanocyclix® technology. We have several case studies of very strong selectivity between extremely close kinases.

Over the years, we have developed our expertise  to further optimize Nanocyclix “probes” as high-quality drug candidates.

Take advantage of Nanocyclix for a program