Off-Target Drug Safety: Replacing Educated Guesswork with Evidence-Based Risk Assessment

Secondary pharmacology profiling involves the screening of small molecule compounds against a broad range of targets in order to try to predict off-target interactions leading to safety issues in humans. To date, this has generally required an opinion-based approach, but opinions vary and are inherently unreliable. To evaluate this quantitatively requires the use of surrogate measures of the level of receptor occupancy required to elicit pharmacodynamic effects at the receptor in humans in vivo. The only universally available data to do this are the minimally effective plasma concentration (unbound) and its relationship to the Ki at the receptor, for clinically used drugs targeting a particular receptor for their clinical efficacy. This webinar will describe how this has been achieved for >100 receptors (G protein-coupled receptors, ion channels, nuclear hormone receptors, enzymes, kinases and transporters) to build a software tool called Secondary Intelligence™.