Discovery and mechanism of action of novel hEag1 potassium channel lead molecules with anti-cancer activity.

Cancer remains an important cause of mortality and economic losses worldwide. For an improved cancer therapy, a permanent need for the discovery of new-generation, refined anticancer agents is needed. Exploitation of genuinely novel classes of cancer targets with new mechanisms of action provides great opportunities for the discovery of new anticancer drugs. Targeting the voltage-gated potassium channel hEag1 in cancer is one of the most exciting recent advances in cancer biology. The Project Consortium aims to discover new selective small-molecule and natural-based inhibitors of hEag1 using drug-design methods and electrophysiological and anticancer evaluation. Proposed Project is an interdisciplinary research project covering all steps of anticancer lead discovery. These include: understanding the genetic and biological basis of cancer, design of new hit compounds, organic synthesis, isolation of new natural hEag1 inhibitors, innovative pharmacological evaluation, and hit-to-lead optimisation. The overarching goal is to discover first-in-class leads for hEag1 cancer target and to broaden treatment possibilities for gastrointestinal carcinomas. Most of the progress in cancer biology of hEag1 and their new modulators have been achieved by Partners that are part of the proposed Project. To create a large innovative force for specific hEag1 anticancer lead discovery, we have designed an interdisciplinary research project that involves all phases of anticancer lead discovery.