TY - JOUR T1 - 11Beta-Hydroxysteroid Dehydrogenase 1 Human Tissue Distribution, Selective Inhibitor and Role in Doxorubicin Metabolism JF - Drug Metabolism and Disposition JO - Drug Metab Dispos DO - 10.1124/dmd.118.081083 SP - dmd.118.081083 AU - Xin Yang AU - Wenyi Hua AU - Sangwoo Ryu AU - Phillip Yates AU - Cheng Chang AU - Hui Zhang AU - Li Di Y1 - 2018/01/01 UR - http://dmd.aspetjournals.org/content/early/2018/04/19/dmd.118.081083.abstract N2 - 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) is mainly distributed 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 faction. Inter-individual variability of 11β-HSD1 is relatively low with about a three-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 thirty-one 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 -