Role of Biotransformation Studies in Minimizing Metabolism-Related Liabilities in Drug Discovery

Metabolism-related liabilities continue to be a major cause of attrition for drug candidates in clinical development. Such problems may arise from the bioactivation of the parent compound to a reactive metabolite capable of modifying biological materials covalently or engaging in redox-cycling reactions leading to the formation of other toxicants. Alternatively, they may result from the formation of a major metabolite with systemic exposure and adverse pharmacological activity. To avert such problems, biotransformation studies are becoming increasingly important in guiding the refinement of a lead series during drug discovery and in characterizing lead candidates prior to clinical evaluation. This article provides an overview of the methods that are used to uncover metabolism-related liabilities in a pre-clinical setting and offers suggestions for reducing such liabilities via the modification of structural features that are used commonly in drug-like molecules

Evaluation of Automated Guided Vehicle Systems for Container Terminals Using Multi Agent Based Simulation

Due to globalization and the growth of international trade, many container terminals are trying to improve performance in order to keep up with demand. One technology that has been proposed is the use of Automated Guided Vehicles (AGVs) in the handling of containers within terminals. Recently, a new generation of AGVs has been developed which makes use of cassettes that can be detached from the AGV. We have developed an agent-based simulator for evaluating the cassette-based system and comparing it to a more traditional AGV system. In addition, a number of different configurations of container terminal equipment, e.g., number of AGVs and cassettes, have been studied in order to find the most efficient configuration. The simulation results suggest that there are configurations in which the cassette-based system is more cost efficient than a traditional AGV system, as well as confirming that multi agent based simulation is a promising approach to this type of applications