Medicinal Chemistry Reviews

Volume 52, Chapter 21

Aldehyde Oxidase Metabolism in Drug Discovery

Aaron C. Burns

1.          Introduction                                                                                                               405

2.         Extensive Metabolism Observed During Clinical Trials                                         406

3.         Structure and Function of Aldehyde Oxidase                                                         408

            3.1        Structural and Mechanistic Aspects                                                             408

            3.2       Substrate Scope                                                                                             409

4.         Variation in Structure, Function and Distribution                                                  410

5.         Identifying and Predicting Aldehyde Oxidase Metabolism                                  411

6.         Strategies to Attenuate Aldehyde Oxidase Metabolism                                        413

            6.1        Androgen Receptor Antagonists                                                                 413

            6.2       Toll-Like Receptor Antagonists                                                                    413

            6.3       Zoniporide Derivatives                                                                                 414

            6.4       Phosphatidylinositol 3-Kinase Inhibitors                                                   415

            6.5       Mesenchymal—Epithelial Transition Factor Inhibitors                             416

            6.6       Deuterium Incorporation: VX-984                                                               416

            6.7       Tropomyosin-Related Kinase Inhibitors                                                     417

7.         Conclusion                                                                                                                 417

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