The ADME Optimization Strategy

The terms druggability and drug-likeness were first introduced by Dr. Christopher Lipinski, who proposed Lipinski s rule of 5 due to the frequent appearance of a number 5 in the rules (Lipinski, 20(X)). The rule of 5 has come to be a compass for the drug discovery industry (Lipinski et al 2(X)1). It stipulates that small-molecule drug candidates should possess  

A compound with fewer than three of these properties is unlikely to become a successful orally bioavailable drug. But like every rule, it has notable exceptions. Such exceptions to Lipinski s rule of 5 that have become marketed drugs are molecules taken up by active transport mechanisms, natural compounds, oligonucleotides, and proteins. 

Pharmacodynamic (PD) effectiveness of test compounds is now routinely assessed initially using a battery in vitro 

While ADME assays and principles are the same, the application of these principles is unique to each drug 

TABLE 7.1 ADME Assays That Inform Toxicity at Different Stages of Drug Discovery and Development 

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