The era of high-quality chemical probes

Small-molecule chemical probes are among the most important tools to study the function of proteins in cells and organisms. Regrettably, the use of weak and non-selective small molecules has generated an abundance of erroneous conclusions in the scientific literature. More recently, minimal criteria have been outlined for investigational compounds, encouraging the selection and use of high-quality chemical probes. Here, we briefly recall the milestones and key initiatives that have paved the way to this new era, illustrate examples of recent high-quality chemical probes and provide our perspective on future challenges and developments.