The Identification of a Group of Self-Assembling, Trimetallic Cryptands with Multi-Kinase Inhibitor Activity Using a Phenotypic Approach to Drug Discovery

Abstract

Despite significant advances in the development of targeted anti-cancer drugs, the much hoped for paradigm shift in cancer survival has been blunted by the emergence of new mechanisms of drug resistance. The development of drugs with multiple mechanisms of action is one approach that has been adopted to circumvent this problem and in this talk, the use of a phenotypic approach to drug discovery based on potency and selectivity in vitro has been used to identify compounds that have multiple mechanisms of action. This talk will specifically focus on the discovery, preclinical activity and mechanism of action of self-assembling trimetallic cryptands that have potent but selective activity against cancer cells in vitro and in vivo.