Panx1 and drug discovery: from non-specific inhibitors to tailored drug compounds

Pannexin (Panx)-1-mediated ATP release has been associated with a broad range of pathological conditions. Conversely, the use of Panx1-inhibitors has shown promising results in the medication of diseases, such as neuroinflammation, melanoma and epilepsy. In addition, Panx1-inhibitors are an indispensable tool for the elucidation of both structure and physiology of Panx1. Over the past years, numerous applications of Panx1-inhibitors have led to new insights into Panx1 influences in health and disease. The major drawback of conventional Panx1-inhibitors, however, is the lack of selectivity resulting in undesired side effects. Nevertheless, these inhibitors are useful resources for drug discovery and lead optimisation approaches have therefore found their way into Panx1 research. Newly developed inhibitors show both high efficacy and selectivity. The combination of drug development and molecular dynamics simulations is a powerful tool to further elucidate both structure and gating mechanisms of Panx1.