Toxicology receptor targeting drugs

At the molecular level, the compound would be screened for activity on the target, for example, receptor binding affinity to cell membranes containing the homologous animal receptors (or if possible, on the cloned human receptors). Early studies would be done to predict effects that might later cause undesired drug metabolism or toxicologic complications. 

This raises the key test of target validation. Does a compound that has the appropriate potency, selectivity, and ADME properties, that is active in "predictive" animal models, and is free of other systems toxicology work in the targeted human disease state This is the ultimate test of a target-based drug discovery program. With the considerable compound attrition rates in moving from animals to diseased humans, this has not proven to be a predictable transition. A case in point is that of the NKl receptor activated by the peptide, substance P. 

Viola, A., Luster, A. D. (2008). Chemokines and their receptors Drug targets in immunity and inflammation. Annual Review of Pharmacology and Toxicology, 48, 171—197. 

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