Pre-clinical drug discovery and

NIH Translational Programs for Assisting Pre-Clinical Drug Discovery and Development... 

The pre-clinical drug discovery process is typically a sequential selection and optimization process focusing, as summarized in Table 2, on different essential properties at each step. " Tool compounds required for early in vitro or in vivo target validation typically do not need to satisfy the same stringent in vivo efficacy and safety criteria as clinical candidates and drugs, which again depend on the targeted therapeutic indication. ... 

Figure 10-1 Alignment of safety profiling, discovery toxicology, and pathology with the pre-clinical drug discovery process8. Profiling assays are implemented according to requirement of the phase, compound availability, and capacity. The complexity is increasing as projects progress toward clinical candidate selection.

The pre-clinical drug development process has as its end product a drug candidate that is suitable for testing in human clinical trials. To achieve this, the candidate must pass pre-clinical toxicology testing, have its adsorption, distribution, metabolism and excretion understood in suitable animal models, and have good scientific evidence that it will provide medicinally beneficial effects. The latter normally requires showing efficacy in animal models of the disease. The early phase discovery process has usually... 

The phases of drug discovery are target finding, hit finding, hit to lead program or lead finding, lead optimization (sometimes pre-clinical candidate selection), and finally clinical candidate selection. 

In addition to the safety studies, extensive investigations must be undertaken to establish the quality of the drug substance and product(s) during the pre-clinical phase. These will usually commence with drug discovery, where the initial characterisation of... 

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