Drug discovery validation

However, the target validation step is unique to target-based drug discovery. 

In the realm of drug discovery, the detection and characterization of target-ligand interactions is a critical process for lead identification, validation, and optimization. 

The popular permeability equations [(7.10) and (7.11)] derived in the preceding section presume that the solute does not distribute into the membrane to any appreciable extent. This assumption may not be valid in drug discovery research, since most of the compounds synthesized by combinatorial methods are very lipophilic and can substantially accumulate in the membrane. Neglecting this leads to underestimates of permeability coefficients. This section expands the equations to include membrane retention. 

Synthetic activity associated with the carbonyl-ene reaction is extensive. During the past decade, the trend has been to perform these reactions in the presence of a Lewis acid in an enantioselective fashion. Efforts to find a general catalyst that affords homoallylic alcohols in high yields and enantioselectivities are continual. The synthetic utility of this reaction has been validated by its application to the synthesis of a number of natural products (see Section 10.12.6) and many structurally novel motifs that have found a place in drug discovery vide infra). It is the latter application that has resulted in research efforts aimed at large-scale production of carbonyl-ene adducts. 

Schuster, D., Laggner, C., Steindl, T.M. and Langer, T. (2006) Development and validation of an in silico P450 profiler based on pharmacophore models. Current Drug Discovery Technologies, 3, 1—48. 

Strachan, R.T., Ferrara, G. and Roth, B.L. (2006) Screening the receptorome an efficient approach for drug discovery and target validation. Drug Discovery Today, 11, 708-716. 

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