Drug Repurposing To Explore Novel Treatment For Cushing Disease

Tech ID: 30335 / UC Case 2019-621-0


UCLA researchers in the Department of Medicine and the Department of Molecular and Medicinal Pharmacology have identified several small molecule reagents to treat Cushing disease.


Cushing disease is a rare disease characterized by excessive adrenal-derived cortisol production, primarily as a result of adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma.  Cushing disease patients have greater propensity to develop osteoporosis, diabetes, cardiovascular disease, and other metabolic diseases.  The first-line treatment of Cushing disease is surgical resection of ACTH-secreting pituitary adenoma, but is limited to microadenomas with <1cm diameter.  Disease recurrence is usually treated with repeated pituitary surgery with <50% success rate, or pituitary-directed radiation therapy that causes hypopituitarism in ~40% patients.  Alternatively, bilateral adrenalectomy resolves hypercortisolism but requires lifelong gluco- and mineralo-corticoid replacement, and may spur rapid pituitary tumor growth in 25% patients.  Thus, there is an unmet medical need in developing treatment for Cushing disease.


Researchers at UCLA have developed a unique highly sensitive and specific “gain of signal” adrenocorticotropic hormone (ACTH) AlphaLISA assay in a rigorous high-throughput screen evaluation.  Using this ACTH AlphaLISA assay in combination with nuclei staining, researchers have identified several compounds that exhibit anti-proliferation effects with IC50 at nanomolar range.  One particular molecule, which belongs to the phosphoinositide 3-kinase (PI3K)/histone deacetylase (HDAC) inhibitor family has demonstrated outstanding performance to block tumor growth and ACTH secretion in both human corticotroph tumor primary cell culture and a Cushing disease xenograft mouse model.


  • Treatment for Cushing disease


  • Both inhibit ACTH secretion to attain eucortisolemia, and block tumor growth
  • The identified compound is deemed non-toxic and well tolerated in humans, as it is being studied in phase II clinical trials for other disease indications
  • Known action mechanism
  • Orally bioavailable

State Of Development

The efficacy has been demonstrated in in vitro and in vivo models of Cushing disease.

Patent Status

Patent Pending


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  • Heaney, Anthony

Other Information


Cushing disease, adrenocorticotropic hormone, ACTH, pituitary adenoma, phosphoinositide 3-kinase inhibitor, histone deacetylase inhibitor, high-throughput screen

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