Data-Driven Exploration of Selectivity and Off-Target Activities of Designated Chemical Probes

Chemical probes are of central relevance for chemical biology. To unambiguously explore the role of target proteins in triggering or mediating biological functions, small molecules used as probes should ideally be target-specific; at least, they should have sufficiently high selectivity for a primary target. We present a thorough analysis of currently available activity data for designated chemical probes to address several key questions: How well defined are chemical probes? What is their level of selectivity? Is there evidence for additional activities? Are some probes “better” than others? Therefore, highly curated chemical probes were collected and their selectivity was analyzed on the basis of publicly available compound activity data. Different selectivity patterns were observed, which distinguished designated high-quality probes.