Physicochemical High Throughput Screening (pC-HTS): Determination of Membrane Permeability, Partitioning and Solubility

Combinatorial and parallel chemistry and genomics in combination with high-throughput screening (HTS) are capable in increasing the number of lead compounds identified in lead discovery programs. Successful application of high-throughputtechnologies in biological screening demonstrates that lead identification itself is often not the time limiting step in drug development. Bottlenecks occur due to missing fast secondary assays as well as the lack of high speed and quality prediction tools. These tools might focus on many aspects of bioavailability such as absorption, protein binding, metabolic stability and toxicity. Although today screening for biological activity is fast, the entire process of lead optimisation is performed in the traditional serial way rather than in parallel (see Figure 1). Future drug discovery and development should preferably proceed with the application of parallel strategies.