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New ACTH-dependent Cushing’s Syndrome drug discovery project launched

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A collaboration between MRC Technology and Prof Adrian Clark and Dr Li Chan at the William Harvey Research Institute, Queen Mary University of London has been launched to develop melanocortin receptor type 2 (MC2R) antagonists for the treatment of ACTH-dependent Cushing’s Syndrome and Congenital Adrenal Hyperplasia (CAH).

MC2R is a G-coupled protein receptor (GPCR) expressed in the adrenal and is a selective receptor for adrenocorticotropic hormone (ACTH). Cushing’s Syndrome is a lethal disease resulting from overproduction of ACTH from a pituitary tumour, leading to glucocorticoid excess and hypertension, diabetes, osteoporosis, susceptibility to infection and tissue fragility. Current treatment aims to remove the source of ACTH by surgery or radiotherapy. In CAH an inherited genetic defect leads to ACTH excess and dysregulated expression of steroid hormones potentially leading to masculinization and hypertension. The ability to antagonize the actions of ACTH in the adrenal would be clinically extremely useful, especially for the period pre- and post surgery, or when patients are waiting for the effects of radiotherapy to become apparent in the case of Cushings syndrome, or in lifelong control of steroid production in CAH.

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