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In the course of the work presented here, new ligands for the SI/II binding site of K-RAS4B were developed starting from bisphenols using various medicinal chemistry concepts. In addition to the determination of structure-activity-relationships (SARs), fragment expansion and PROTAC-design were used as further concepts. Computational calculations were used for the identification of active compounds via docking studies and e-learning algorithms. The compounds, most of which were synthesized, were subsequently investigated by the project partners with respect to their binding to K-RAS4B, their influences on underlying biochemical reactions and on cellular effects.