Academy of Integrative Medicine, College of Pharmacy, The National & Local Joint Engineering Research Center for Drug Development of Neurodegenerative Disease, Dalian Medical University, Dalian 116044, PR China.
Preparation Department, Ningxia Hui Autonomous Region Hospital of Traditional Chinese Medicine, Yinchuan 750021, PR China.
Future Med Chem. 2019 Nov;11(22):2891-2903. doi: 10.4155/fmc-2019-0173. Epub 2019 Nov 8.
CYP3A5 plays a vital role in the drug metabolism, it displays varied expression levels among individuals and is easily influenced by genetic polymorphisms and some diseases. A dual function probe isobutyryl-11-keto--boswellic acid (IKBA) was developed; it possessed a high selectivity toward CYP3A5 and CYP3A enzymes for its two individual metabolites, respectively. The probe has the high accuracy and wide applicability in measuring the real activity of CYP3A5. Finally, IKBA was successfully used for the evaluation of the activity of CYP3A5 and CYP3A enzymes in various bio samples. IKBA could serve as a useful tool for exploring the physiology and pathology functions of CYP3A5 and give some useful guidance for the rational use of clinical drugs.
CYP3A5 在药物代谢中起着至关重要的作用，其在个体间表达水平存在差异，并且容易受到遗传多态性和某些疾病的影响。我们开发了一种双功能探针异丁酰-11-酮-β-乳香酸（IKBA），它的两种单独代谢产物分别对 CYP3A5 和 CYP3A 酶具有很高的选择性。该探针在测量 CYP3A5 的真实活性方面具有很高的准确性和广泛的适用性。最后，我们成功地将 IKBA 用于评估各种生物样本中 CYP3A5 和 CYP3A 酶的活性。IKBA 可以作为探索 CYP3A5 的生理学和病理学功能的有用工具，并为临床药物的合理使用提供一些有用的指导。
