Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee
Drug Metab Dispos. 2024 May 16;52(6):493-497. doi: 10.1124/dmd.123.001431.
Although the mention of cytochrome P450 (P450) inhibition usually brings to mind unwanted variability in pharmacokinetics, in several cases P450s are good targets for inhibition. These P450s are essential, but in certain disease states, it is desirable to reduce the concentrations of their products. Most of the attention to date has been with human P450s 5A1, 11A1, 11B1, 11B2, 17A1, 19A1, and 51A1. In some of those cases, there are multiple drugs in use, e.g., exemestane, letrozole, and anastrozole with P450 19A1, the steroid aromatase target in breast cancer. There are also several targets that are less developed, e.g., P450s 2A6, 8B1, 4A11, 24A1, 26A1, and 26B1. SIGNIFICANCE STATEMENT: The selective inhibition of certain cytochrome P450s that have major physiological functions has been shown to be very efficacious in certain human diseases. In several cases, the search for better drugs continues.
虽然提到细胞色素 P450（P450）抑制通常会让人联想到药代动力学的不必要变异性，但在某些情况下，P450 是抑制的良好靶点。这些 P450 是必需的，但在某些疾病状态下，降低其产物的浓度是可取的。迄今为止，大多数关注的焦点都集中在人类 P450 5A1、11A1、11B1、11B2、17A1、19A1 和 51A1 上。在其中一些情况下，有多种药物在使用，例如，与 P450 19A1 一起使用的 exemestane、letrozole 和 anastrozole，这是乳腺癌中甾体芳香酶的靶标。还有一些靶标开发得较少，例如 P450 2A6、8B1、4A11、24A1、26A1 和 26B1。重要性声明：选择性抑制某些具有主要生理功能的细胞色素 P450 已被证明在某些人类疾病中非常有效。在某些情况下，人们仍在寻找更好的药物。
