TY - JOUR T1 - 11<em>β</em>-Hydroxysteroid Dehydrogenase 1 Human Tissue Distribution, Selective Inhibitor, and Role in Doxorubicin Metabolism JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1023 LP - 1029 DO - 10.1124/dmd.118.081083 VL - 46 IS - 7 AU - Xin Yang AU - Wenyi Hua AU - Sangwoo Ryu AU - Phillip Yates AU - Cheng Chang AU - Hui Zhang AU - Li Di Y1 - 2018/07/01 UR - http://dmd.aspetjournals.org/content/46/7/1023.abstract N2 - 11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) is distributed mainly in the human liver, with no detectable levels in the intestine or kidney, based on a newly developed proteomic approach. 11β-HSD1 is mostly membrane-bound and retained in the liver microsomal fraction. Interindividual variability of 11β-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 11β-HSD1 protein expression or activity based on data from 31 donors. PF-915275 has been identified as a selective 11β-HSD1 inhibitor with minimal effects on carbonyl reductase 1 and major cytochrome P450 enzymes. 11β-HSD1 has been shown, for the first time, to be involved in doxorubicin metabolism, accounting for approximately 30% of doxorubicinol formation in human hepatocytes. ER -