Beware of ligand efficiency (LE): understanding LE data in modeling structure-activity and structure-economy relationships.

Background: On the one hand, ligand efficiency (LE) and the binding efficiency index (BEI), which are binding properties (B) averaged versus the heavy atom count (HAC: LE) or molecular weight (MW: BEI), have recently been declared a novel universal tool for drug design. On the other hand, questions have been raised about the mathematical validity of the LE approach.

Results: In fact, neither the critics nor the advocates are precise enough to provide a generally understandable and accepted chemistry of the LE metrics.

Between Descriptors and Properties: Understanding the Ligand Efficiency Trends for G Protein-Coupled Receptor and Kinase Structure-Activity Data Sets.

The chemical meaning of the ligand efficiency (LE) metrics is explained in this paper using a large G protein-coupled receptor (GPCR) and kinase structure-activity (IC, K) data set. Although there is a controversy in the literature regarding both the mathematical validity and the performance of LE, it is in common use as an early estimator for drug optimization. Apparently, the numerous con arguments are not convincing enough.

The analysis of the market success of FDA approvals by probing top 100 bestselling drugs.

Target-oriented drug discovery is the main research paradigm of contemporary drug discovery. In target-oriented approaches, we attempt to maximize in vitro drug potency by finding the optimal fit to the target. This can result in a higher molecular complexity, in particular, the higher molecular weight (MW) of the drugs.

Top 100 bestselling drugs represent an arena struggling for new FDA approvals: drug age as an efficiency indicator.

We analyzed a list of the top 100 bestselling drugs as a struggling market for new FDA approvals. Using the time from drug approval by the FDA as a measure of drug age, our analysis showed that the top 100 bestselling drugs are getting older. This reflects the stalled launch of new drugs into the market during recent years.