Exploring chemical space with organometallics: Ruthenium complexes as protein kinase inhibitors

Complementing organic elements with a metal center provides new opportunities for building three-dimensional structures with unique and defined shapes. Such access to unexplored chemical space may lead to the discovery of molecules with unprecedented properties. Along these lines, this account article describes our successful design of highly potent and selective ruthenium-based inhibitors for the protein kinases GSK-3 and Pim-1 by using the class of indolocarbazole alkaloids as a lead structure. The described ruthenium complexes are kinetically inert scaffolds in which the ruthenium has the function to organize the orientation of the organic ligands in the three-dimensional space.