Molecular assays target site

In summary, based on the observation of divergent in vitro and in vivo SAR, a new class of cholesterol-lowering compounds was discovered. Subsequent biological characterization of the first generation lead compound SCH-48461, limited the site of action to be at or near the intestinal villi, with the most probable mechanism being the inhibition of luminal absorption. An SAR optimization based solely on an in vivo assay and without biochemical characterization of the molecular target led to the design of ezetimibe (1). 

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