KISSf is is a high throughput screening facility for the identification and of caracterization of news proteins kinases inhibitors. Following, the works led on the first stage of cellular division on sea urchins embryos and starfish oocytes, the team focused its efforts on several protein kinase families potentially relevant for the treatment of several human diseases such as cancer. Our research work describes the role of protein kinases involved in the mechanisms of cellular proliferation as well as the mode of action and the selectivity of their inhibitors. Among these kinases, the cycline-dependent kinases (CDKs) were widely studied because of their essential roles in biological processes and their implication in numerous pathologies. CDKs inhibitors have particular properties: on one hand, they trigged tumoral cell death by apoptosis ((by a mechanism involving Mcl-1 or others factors of survival) and on the others hand, they show protective effects towards neuronal healthy cells involving CDK5). These studies have allowed the identification, the optimization and the characterization of many protein kinase inhibitor families kinases such as: oloumocine, roscovitine, purvalanol, paullones, indirubines, hymenialdisine, meridianines, meriolines. The key molecule is the (R)-roscovitine actually in phase2b for the treatment of syndrome de Cushing (chronical hypercortisolisme ).
The strategy followed by KISSf for the research of inhibitors of proteins kinases is to identify ATP mimetic compounds (type I inhibitors) able to bind the ATP pocket of the enzyme. The fact that there is structural variability on this particular site from a kinase to another makes it possible to find specific inhibitors.
Chemical inhibitors characterized by KISSf are either potential new therapeutic molecules or tools for fundamental research to help understand the protein kinases cellular functions (chemical biology).