Discovery phase, candidate screening

Automated online SPE systems have been applied to various phases of drug discovery. McLoughlin et al. (1997) utilized the Prospekt system in pharmacokinetic animal studies for rapid drug candidate screening. Up to 10 compounds were simultaneously monitored. The lower limits of detection were... 

After the hit discovery process (often using high-throughput screening), early drug discovery is generally split into a hit to lead phase and a lead optimization phase, followed by the selection of development candidates (DCs) (Figure 12.2). In vitro... 

PURPOSE AND RATIONALE In vitro testing of drug candidates and combinatorial chemistry lead to an increase of lipophilic compounds with poor solubility (Lipinsky). Poor solubility itself may lead to poor oral availability of a potential drug. The growing demand for solubility data in lead phase of drug discovery is answered by a variety of simple solubility assays, which allow the classification of a compound without real quantification (see previous section). One of the easiest way to detect saturation in a solvent is the turbidity of the solution if precipitation occurs. The turbidity caused by precipitation of a poorly soluble compound can be detected by a couple of detection methods (Van de Hulst, Hongve). Lipinsky describes the first methodology, which use UV as detection method and is able to screen hundreds of compounds a day with one instrument. 

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