Drug Metabolism in Preclinical Drug Development: A Survey of the Discovery Process, Toxicology, and Computational Tools.

Background: While establishing efficacy in translational models and humans through clinically-relevant endpoints for disease is of great interest, assessing the potential toxicity of a putative therapeutic drug is critical. Toxicological assessments in the pre-clinical discovery phase help to avoid future failure in the clinical phases of drug development. Many in vitro assays exist to aid in modular toxicological assessment, such as hepatotoxicity and genotoxicity.

Prediction of Chemical Multi-target Profiles and Adverse Outcomes with Systems Toxicology.

The field of systems biology, termed systems toxicology when applied to the characterization of adverse outcomes following chemical exposure, seeks to develop biological networks to explain phenotypic responses. Ideally, these are qualitatively and quantitatively similar to the actual network of biological entities that have functional consequences in living organisms. In this review, computational tools for predicting chemicalprotein interactions of multi-target compounds are outlined.

Aflibercept: A Review of Its Use in the Management of Diabetic Eye Complications.

Aflibercept is the most recently approved vascular endothelial growth factor (anti-VEGF) inhibitor for the management of diabetic macular edema and diabetic retinopathy. The purpose of this article is to review the efficacy and safety of aflibercept in the management of diabetic eye complications and to describe its place in therapy. Anti-VEGF agents have been noted in clinical trials to be superior to laser photocoagulation, the standard therapy ( P < .