The problem of racemization in drug discovery and tools to predict it

Introduction: Racemization has long been an ignored risk in drug development, probably because of a lack of convenient access to good tools for its detection and an absence of methods to predict racemization risk. As a result, the potential effects of racemization have been systematically underestimated.

Areas covered: Herein, the potential effects of racemization are discussed through a review of drugs for which activity and side effects for both enantiomers are known. Subsequently, drugs known to racemize are discussed and the authors review methods to predict racemization risk. Application of a method quantitatively predicting racemization risk to databases of compounds from the medicinal chemistry literature shows that success in clinical trials is negatively correlated with racemization risk.

Expert opinion: It is envisioned that a quantitative method of predicting racemization risk will remove a blind spot from the drug development pipeline. Removal of the blind spot will make drug development more efficient and result in less late-stage attrition of the drug pipeline.