Targeted potency

Drug CYP Pharmacological target CYP potency (pM) Target potency (pM) Potency ratio DDI magnitude... 

Number of Locations Mean Potency (% Target) Potency Range (% Target) RSD (%)... 

Lead optimization involves more than just optimizing for target potency. New technology allows early lead optimization campaigns to address and consider multiple parameters and inputs for each round of iterative library synthesis. These inputs allow for the rapid development of potent compounds with drug-like profiles, as opposed to just potent compounds. These data also provide quick kills to individual leads or series and allow the lead optimization effort to re-direct resources toward more productive leads (1-5, 8-20). 

Williams s third objection to the standard deviation is that it is misleading when applied to mixtures of different compositions. He suggested, rather, the coefficient of variation, which eliminates the bias from variations in the level of target potency. 

Is the molecule active at primary target (Potency and efficacy.)... 

Compound Structure Targets Potency PDBs for target References... 

The Cmax is an important parameter in predicting margins versus some key off target potencies, such as hERG inhibition, and assuming instantaneous absorption is given by eqn (13.15). We found Cmax could also be predicted within 2-fold of the clinically observed value, as shown in Figure 13.5." ... 

The failure of all other important properties to stay put while one of them is optimized means that linear optimization (first target potency, then perhaps selectivity against an antitarget, then solubility, etc.) is just not an option. It would be nice and straightforward... 

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