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Glucuronidation catalyzed by uridine 5′-diphospho-glucuronosyltransferase (UGT) is the most common phase II metabolism. The UGTs can severely limit a drug's exposure and generate reactive metabolites, leading to toxicity. This chapter provides a brief overview of the current understanding of the UGT enzyme family, followed by various medicinal chemistry strategies to address this metabolic liability and select examples from the literature.

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