Session Speaker

Chemistry Driven Drug Discovery With The Nested Chemical Library Of Kinase Inhibitors
György Kéri, Zoltán Varga, Zoltán Greff, János Pato, Bálint Szokol, Zoltán Horváth, László Örfi Henrik Daub, Axel Ullrich

The multiple target approach of kinase inhibitors has become recently a very important approach in signal transduction therapy. We have developed a Nested Chemical Library™ of kinase inhibitors for hit/lead finding against selected kinases or multiple targets. Novel and potential kinase targets can be validated chemically by using our Chemical Validation Library compounds. The selected and active inhibitors of a particular kinase are applied to therapeutically relevant cellular assays, in order to confirm the role of the kinase activity in this biological model. If the hits are not drug like and are in a heavily patented field, we perform a scaffold hopping technique to identify novel lead structures. We use our pharmacophore modeling technique including the computational screening of our 15 million compound synthesizable virtual library and our medicinal chemistry expertise to come up with novel patentable scaffolds. Our Master keys can also be the starting points for novel patentable scaffolds. We have sub-micromolar inhibitors against 124 kinases and developed lead molecules against various oncological and infectious disease targets including Tuberculosis, HIV and Influenza. We have developed a sophisticated chemical derivatization based affinity chromatography technology for selectivity profiling and off-target identification of kinase inhibitors.