Combinatorial Chemistry and High Throughput Screening

Great efficiencies have been achieved in drug discovery as a result of technological advances in target identification, high throughput screening, high throughput organic synthesis, just-in-time in vitro ADME (Absorption, Distribution, Metabolism and Excretion), early pharmacokinetic screening and early toxicity screening (e.g., hERG) of drug leads. The field of combinatorial chemistry emerged in the early 1990s as a means for chemists to synthesize compounds more efficiently and more economically. Owing to the shear numbers of compounds afforded by combinatorial chemistry and more specifically, parallel solution and solid phase organic synthesis, innovations were required for their evaluation in both biological and ADME assays. High throughput, miniaturized biological screening assays were established and allowed for rapid, high quality evaluation of these compound collections. Similarly, high throughput ADME and pharmacokinetic techniques were introduced (most notably LC/MS/MS) so as to optimize the compounds, not only for biological activity, but for their “drug-ability” as well. More recently, high throughput techniques to optimize the safety of the compounds have been introduced. All of these tools have now become indispensable in the discovery setting and the fruits of these new innovations are now being realized. Compounds are advancing to pre-clinical and early clinical development at an unprecedented rate and this can be attributed, in no small measure, to these technological innovations in drug discovery. Many of these areas will be highlighted in this symposium.