Lipophilic efficiency

Lipophilic efficiency[1] (LiPE), sometimes referred to as ligand-lipophilicity efficiency (LLE) is a parameter used in drug design and drug discovery to evaluate the quality of research compounds, linking potency and lipophilicity in an attempt to estimate druglikeness.

[4][5] On the other hand, LogP is an 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, lack of selectivity and non-specific toxicity.

[6] 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 capturing 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.

An alternative equation uses the logarithm of the ratio of potency (measured as binding energy) and the partition coefficient to compute a lipophilic ligand efficiency index (LE) with a different scale.

A plot of LogP vs pIC 50 for 2 series of compounds (series 1: green dots, series 2: blue dots). Diagonal lines represents areas of equal LiPE. Analysis of this LiPE plot shows that series 1 includes many compounds with a high LiPE, and thus may represent a better lead series for further optimization.