Drug efficiency: a new concept to guide lead optimization programs towards the selection of better clinical candidates

Abstract

As a result of their wide acceptance and conceptual simplicity, drug-like concepts are having a major influence on the drug discovery process, particularly in the selection of the ‘optimal’ absorption, distribution, metabolism, excretion and toxicity and physicochemical parameters space. While they have an undisputable value when assessing the potential of lead series or in evaluating inherent risk of a portfolio of drug candidates, they result much less useful in weighing up compounds for the selection of the best potential clinical candidate. We introduce the concept of drug efficiency as a new tool both to guide the drug discovery program teams during the lead optimization phase and to better assess the developability potential of a drug candidate.

Keywords::

• ADMET
• biophase
• CNS
• developability
• drug discovery
• ligand efficiency
• pharmacodynamics
• pharmacokinetics
• physicochemical properties
• volume of distribution

Acknowledgments

The authors thank M Bayliss, P Eddershaw, M Briggs, M Pellegatti and S Clark for discussions on the subject matter.

Notes