Nanocyclix is a kinase focused library of small macrocyclic hinge binder molecules. This library was designed using a chemocentric approach to identify attractive and selective kinases inhibitors. All the compounds are in the drug-like properties space and hit compounds display nanomolar potencies and excellent selectivity against a small number of kinases.

Nanocyclix design is based on the macrocyclisation paradigm of known hinge binder scaffolds resulting in tighter binding site recognition, potency and selectivity towards the ATP site. Exploring different lengths and functionalities of the cyclic linker allow populating the conformational space of every template in order to identify an optimal match between the size and mobility of the binding site and the macrocyclic ligand. Potent and selective inhibitors of therapeutic kinases such as LRRK2, RIPK2 and ALK1 have been identified by this approach and their optimization to advanced lead will be briefly described.