11 β -Hydroxysteroid Dehydrogenase 1 Human Tissue Distribution, Selective Inhibitor, and Role in Doxorubicin Metabolism.

11 β -Hydroxysteroid dehydrogenase 1 (11 β -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 β -HSD1 is mostly membrane-bound and retained in the liver microsomal fraction. Interindividual variability of 11 β -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 β -HSD1 protein expression or activity based on data from 31 donors. PF-915275 has been identified as a selective 11 β -HSD1 inhibitor with minimal effects on carbonyl reductase 1 and major cytochrome P450 enzymes. 11 β -HSD1 has been shown, for the first time, to be involved in doxorubicin metabolism, accounting for approximately 30% of doxorubicinol formation in human hepatocytes.