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Osilodrostat: 11β-hydroxylase inhibitor for treatment of Cushing's disease
1Professor Emeritus of Pharmacology, University of Auckland, Auckland, New Zealand and Professor Emeritus of Oral Biology, Edmonton, Alberta, Canada. dmpaton62@gmail.com.
Abstract:
Osilodrostat was synthesized in a search for a drug that would inhibit the synthesis of aldosterone, with the aim to discover a new approach for treating hypertension. However, early clinical trials revealed that the doses that could be used for this purpose were limited because osilodrostat was also inhibiting the synthesis of cortisol. Osilodrostat is in fact an inhibitor of both the cytochrome P450 (CYP) enzymes 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) and thus inhibits the synthesis of both cortisol and aldosterone. Subsequent clinical trials have established that it can be used very effectively in Cushing's disease caused by a functioning tumor of the pituitary gland in patients whose condition has not been adequately treated by surgery or who are not candidates for such surgery.
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