New and emerging drug therapies for Cushing’s disease.

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New and emerging drug therapies for Cushing's disease.

Expert Opin Pharmacother. 2018 Jul 26;:1-14

Authors: Störmann S, Schopohl J

Abstract
INTRODUCTION: Cushing's disease is a rare systemic and disabling disease due to oversecretion of adrenocorticotrophic hormone (ACTH) resulting in excess cortisol levels. Diagnosis and treatment are difficult; despite the availability of various pharmaceutical treatment options, there is an ongoing, unmet need for even more effective treatment. Areas covered: The present review aims at providing an overview of available drugs and presenting new developments. Focusing on the pituitary as a target, the review covers compounds targeting pituitary cell signaling or cell cycle control such as heat shock protein inhibitors (e.g. silibinin), histone deacetylase inhibitors (trichostatin A, vorinostat), kinase inhibitors (gefitinib, seliciclib), and others (such as triptolide, AT-101). Levoketoconazole and osilodrostat are in clinical testing and inhibit steroidogenesis. Blockade of ACTH receptor binding at the adrenal level is explained as a theoretical drug target. Inhibition of binding of the glucocorticoid receptor in the peripheral tissue plays a minor role due to its lack of biomonitoring options. Expert opinion: In our opinion, further research and drug development of pituitary-directed targets are necessary. Combination therapies may exert synergistic effects and allow for smaller and better tolerated doses, but more experience and data are needed to guide such treatment schemes.

PMID: 30048162 [PubMed - as supplied by publisher]

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