Lipophilic efficiency
Lipophilic efficiency sometimes referred to
as ligand-lipophilicity efficiency (LLE) is a parameter used in drug design
Drug design
Drug design, also sometimes referred to as rational drug design or structure-based drug design, is the inventive process of finding new medications based on the knowledge of the biological target...

 and drug discovery
Drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...

  to evaluate the quality of research compounds, linking potency and lipophilicity in an attempt to estimate druglikeness
Druglikeness is a qualitative concept used in drug design for how "druglike" a substance is with respect to factors like bioavailability. It is estimated from the molecular structure before the substance is even synthesized and tested...

. For a given compound LiPE is defined as the pIC50
The half maximal inhibitory concentration is a measure of the effectiveness of a compound in inhibiting biological or biochemical function. This quantitative measure indicates how much of a particular drug or other substance is needed to inhibit a given biological process by half...

 (or pEC50
The term half maximal effective concentration refers to the concentration of a drug, antibody or toxicant which induces a response halfway between the baseline and maximum after some specified exposure time...

) of interest minus the LogP of the compound.

In practice, the calculated value cLogP is often used instead of the measured LogP.
LiPE is used to compare compounds of different potencies (pIC50s) and lipophilicities (LogP). High potency (high value of pIC50) is a desirable attribute in drug candidates, as it reduces the risk of non-specific, off-target pharmacology at a given concentration. When associated with low clearance, high potency also allows for low total dose, which lowers the risk of idiosyncratic drug reaction
Idiosyncratic drug reaction
Idiosyncratic drug reactions, also known as type B reactions, are drug reactions that occur rarely and unpredictably amongst the population. This is not to be mistaken with idiopathic, which implies that the cause is not known...


On the other hand, LogP is a estimate of a compound's overall lipophilicity, a value that influence its behavior in a range of biological processes relevant to a drug discovery, such as solubility, permeability through biological membranes, hepatic clearance
A clearance can refer to:* in chess, A positional move, where a player moves a piece occupying a certain square away, replacing it with an allied piece that will strengthen the player's position....

, lack of selectivity and non-specific toxicity. For oral drugs, a LogP value comprised between 2 and 3 is often considered optimal to achieve a compromise between permeability and first-pass clearance.

LiPE allows to capture both values in a single parameter, and empirical evidence suggest that quality drug candidates have a high LiPE (>6); this value corresponds to a compound with a pIC50 of 8 and a LogP of 2. Plotting LogP against pIC50 for a range of compounds allows to rank series and individual compounds.
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