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This lecture delves into the complexities of Drug-Induced Liver Injury (DILI), a major safety concern in drug development. It covers the mechanisms of DILI, the role of cytochrome P450 enzymes, and the importance of Phase I and Phase II detoxification pathways. The instructor discusses case studies, such as the hepatotoxicity of acetaminophen and the structural alerts for potential DILI. The lecture also explores strategies to mitigate DILI, including Structure-Metabolism Relationship (SMR) studies and the importance of understanding reactive metabolites. Students will gain insights into the challenges of drug development and the critical role of liver metabolism in drug safety.