ADME Profiles and Physical Properties

Further analyses of large proprietary databases have focused on matched pair analysis of phenyl substituent effects on metabolic stability and on cytochrome P450, hERG inhibition, solubility and artificial membrane permeability. These studies also show that substituent lipophilicity is the dominant driver of ADMET properties. However, because of the opposing effects of physical properties (for example on solubility and permeability) there are no perfect substituents, where all ADMET properties are improved at 

The therapy class of a drug can play a role in determining its physical properties, especially where there are specific permeability requirements. Thus drugs that act on the central nervous system (CNS) have to cross the blood-brain barrier and have lower and mol. wt than their non-CNS 

Screening has had less success in the anti-infective area than others and the natural world may remain a good source of future anti-infective agents. 

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