Grant: Operating Grant

The discovery and development of new drugs with better therapeutic efficacy and lesser undesirable effects remains an unmet need for many clinical indications. In recent years, the rate of discovery and commercialization of truly innovative drugs has sensibly decreased. Many factors contribute to this biopharmaceutical crisis but one of the causes is certainly that the low hanging fruits have already been harvested. In other words, a significant number of drugs acting in conventional ways by directly binding to and inhibiting or activating enzymes, channel or receptors have already been developed and, improving on that theme is increasingly challenging. Obviously, improving on drugs directly inhibiting or activating conventional therapeutic targets is still needed. However, taking advantage of recent knowledge on how potential drug targets can be controlled in novel ways will be essential to create the next generation of drugs. New findings on one of the most prominent family of drug targets, the G protein coupled receptors (GPCRs), indicate that many cellular factors can regulate their activity. Targeting these processes offers new opportunities for the development of innovative therapeutic agents. Therefore, the present proposal aims at further understanding the mechanisms regulating the activity of GPCRs with the intention of identifying novel regulatory process that could be pharmacologically targeted for therapeutic purposes. The studies proposed also include the search for new chemical entities that will serve as tool to better probe the role of the various mechanisms unravelled and could represent interesting lead candidates for the development of new classes of drugs for various diseases.