Optimizing the hit-to-lead process using SPR analysis.

Secondary screening and lead optimization, where a large number of "hit" compounds are refined to a viable set of "lead" drug candidates, are considered to be bottlenecks to the drug discovery process and are targets for streamlining. Surface plasmon resonance (SPR) is a nonlabel technology that can generate kinetic data on biomolecular interactions. This allows researchers to quantitate the binding characteristics of lead compounds with their targets in terms of affinity, specificity, and association/dissociation rates in parallel. The latest generation of SPR biosensors integrate the hit-to-lead process and generate a greater depth of information, providing answers that cannot be addressed by traditional end-point assays. This allows users to make more informed choices on the selection of candidate molecules prior to preclinical development. A number of studies have used SPR biosensors in secondary screening, lead optimization, quantitative structure-activity relationship analysis, and predictive adsorption, distribution, metabolism, excretion, and/or toxicity evaluations.