Pharmacokinetics, Dynamics and Metabolism (X.Y., W.H., S.R., H.Z., L.D.) and Clinical Pharmacology (C.C.), Pfizer Inc., Groton, Connecticut; and Early Clinical Development, Pfizer Inc., Cambridge, Massachusetts (P.Y.).
Pharmacokinetics, Dynamics and Metabolism (X.Y., W.H., S.R., H.Z., L.D.) and Clinical Pharmacology (C.C.), Pfizer Inc., Groton, Connecticut; and Early Clinical Development, Pfizer Inc., Cambridge, Massachusetts (P.Y.)
Drug Metab Dispos. 2018 Jul;46(7):1023-1029. doi: 10.1124/dmd.118.081083. Epub 2018 Apr 19.
11-Hydroxysteroid dehydrogenase 1 (11-HSD1) is distributed mainly in the human liver, with no detectable levels in the intestine or kidney, based on a newly developed proteomic approach. 11-HSD1 is mostly membrane-bound and retained in the liver microsomal fraction. Interindividual variability of 11-HSD1 is relatively low, with about a 3-fold difference. A significant correlation was not observed between various demographic variables (ethnicity, gender, age, weight, smoking, and alcohol use) and 11-HSD1 protein expression or activity based on data from 31 donors. PF-915275 has been identified as a selective 11-HSD1 inhibitor with minimal effects on carbonyl reductase 1 and major cytochrome P450 enzymes. 11-HSD1 has been shown, for the first time, to be involved in doxorubicin metabolism, accounting for approximately 30% of doxorubicinol formation in human hepatocytes.
11-羟类固醇脱氢酶 1（11-HSD1）主要分布于人体肝脏，根据新开发的蛋白质组学方法，在肠道或肾脏中无法检测到。11-HSD1 主要是膜结合的，并保留在肝微粒体部分。个体间 11-HSD1 的变异性相对较低，差异约为 3 倍。31 位供体的数据显示，各种人口统计学变量（种族、性别、年龄、体重、吸烟和饮酒）与 11-HSD1 蛋白表达或活性之间没有显著相关性。PF-915275 已被确定为选择性 11-HSD1 抑制剂，对羰基还原酶 1 和主要细胞色素 P450 酶的影响很小。11-HSD1 首次被证明参与阿霉素代谢，在人肝细胞中占阿霉素醇形成的约 30%。
