Group Efficiency: A Guideline for Hits‐to‐Leads Chemistry

Herein we describe the concept of group efficiency (GE), which is an extension of ligand efficiency (LE), that we find particularly useful during the hit-tolead and optimisation stages of drug discovery projects. LE has already become popular amongst medicinal chemists. It is used to normalise the binding affinity of a compound with respect to its molecular weight and is a simple way to rank and compare the affinities of compounds with different sizes. The term LE was first suggested by Hopkins et al. as a measure of the free energy of binding (DGb) divided by the molecular size and is related to a publication from Kuntz et al. :