Professor Christian Pfeifer will talk about the discovery of a new photo-cleavable prodrug technology that could find broad applications.
Protein kinases are one of today's most important targets in oncology and also in drug discovery, because of their many roles in regulating cellular growth and survival. Abnormal kinase activity can often be the cause of e.g. cancer, where kinases regulate many aspects that control cell proliferation, migration and apoptosis. In spite of the efficacy of drugs on the market (e.g. Gleevec/Imatinib and iressa/Gefitinib), there is an immense activity in research and discovery for new drugs that inhibit specific kinases such as tyrosin kinases.
Abstract
Among human protein kinases (PK) as validated drug targets in oncology, receptor tyrosine kinases including VEGFR, PDGFR and c-kit are considered to be key for the development of clinically effective inhibitors. In PK the molecular binding site of most inhibitors is the highly conserved ATP binding pocket. Herein, small molecular differences in amino acid identity provide selectivity filters for specific inhibitor design. In our Medicinal Chemistry projects and lead optimization strategies using structure-based design we developed highly potent PK inhibitors with IC50 values in the nM range and also showing cellular efficacy. These compounds but also approved drugs were taken further for innovative photoactivatable “caged” prodrug concepts.