School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061-0293, Japan.
School of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 1757 Kanazawa, Tobetsu-cho, Ishikari-gun, Hokkaido 061-0293, Japan.
Bioorg Med Chem Lett. 2023 Apr 15;86:129206. doi: 10.1016/j.bmcl.2023.129206. Epub 2023 Mar 6.
Cytochrome P450 2A6 (CYP2A6) inhibitors are expected to be suitable as smoking cessation aids and for cancer prevention. Because the typical coumarin-based CYP2A6 inhibitor methoxsalen also inhibits CYP3A4, unintended drug-drug interactions are still a concern. Therefore, the development of selective CYP2A6 inhibitors is desirable. In this study, we synthesized coumarin-based molecules, determined the IC values for CYP2A6 inhibition, verified the possibility of mechanism-based inhibition, and compared the selectivity for CYP2A6 versus CYP3A4. The results demonstrated that we developed CYP2A6 inhibitors that were more potent and selective than methoxsalen.
细胞色素 P450 2A6（CYP2A6）抑制剂有望成为戒烟辅助药物和癌症预防药物。由于典型的香豆素类 CYP2A6 抑制剂甲氧沙林也抑制 CYP3A4，因此仍然存在潜在的药物相互作用问题。因此，开发选择性 CYP2A6 抑制剂是可取的。在这项研究中，我们合成了香豆素类分子，确定了 CYP2A6 抑制的 IC 值，验证了基于机制的抑制的可能性，并比较了 CYP2A6 与 CYP3A4 的选择性。结果表明，我们开发的 CYP2A6 抑制剂比甲氧沙林更有效和选择性。
