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Inhibitors of 11β-Hydroxylase (CYP11B1) for Treating Diseases Related to Excess Cortisol

[ Vol. 23 , Issue. 6 ]

Author(s):

Weixing Zhu, Zhuo Chen, Qianbin Li, Guishan Tan and Gaoyun Hu   Pages 623 - 633 ( 11 )

Abstract:


The overproduction of cortisol is associated with many severe and life-threatening diseases, such as Cushing’s syndrome (CS) and chronic wound healing. 11β-Hydroxylase (CYP11B1) is considered as an attractive target for treating these diseases, since it is a key enzyme responsible for the last step in cortisol biosynthesis. Nowadays, medical therapy has become increasingly important for CS patients, especially for those who are in need of surgery or suffer from surgery failure and those in early phases of radiation therapy. In clinic, steroidogenesis blockers including CYP11B1 inhibitors are utilized most frequently. Nevertheless, drugs that inhibit CYP11B1 are inevitable with side effects due to lack of selectivity over other steroidogenesis enzymes. Recent advances in the development of novel CYP11B1 inhibitors might overcome these limitations. In addition, the beneficial effects of down-regulation of cortisol levels to wound closure have been recently disclosed and have stimulated topical application of CYP11B1 inhibitors as a novel therapeutic strategy for curing chronic wounds. Herein, we provide a review of the current CYP11B1 inhibitors in clinic combating CS and the latest development of novel CYP11B1 inhibitors for treating CS and chronic wounds.

Keywords:

Inhibitors of 11β-hydroxylase, cortisol, chronic wound healing, Cushing’s syndrome, steroidogenesis blockers, inhibitors of aldosterone synthase, cortisol related diseases.

Affiliation:

, , , Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Central South University, 410013, Changsha, Hunan, China.



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