Seliciclib (R-roscovitine or CYC202) is an investigational medicine being developed by Cyclacel for the treatment of Cushing’s disease. Seliciclib also is being investigated as a potential therapy for several cancers, rheumatoid arthritis (RA), and cystic fibrosis (CF).
How Seliciclib works
Cushing’s disease is caused by a tumor in the pituitary gland stimulating the production of excessive adrenocorticotropic hormone (ACTH), which triggers the production and release of cortisol from the adrenal gland. To produce ACTH, the precursor proopiomelanocortin (POMC) gene is required.
Seliciclib is a cell cycle inhibitor that aims to target the tumor in the pituitary gland. It acts to block cyclin-dependent kinase 2 (CDK2) and cyclin E, which are normally involved in regulating cell growth. By inhibiting these two targets, Seliciclib may be able to control, or shrink, the pituitary tumor by blocking cell growth.
Furthermore, cyclin E expression is higher in Cushing’s disease tumors, and also is involved in signaling pathways to produce more POMC and therefore ACTH. By inhibiting cyclin E, it could reduce ACTH and cortisol levels, alleviating the symptoms of Cushing’s disease.
Seliciclib in clinical trials
Cyclacel has carried out 16 clinical trials with Seliciclib, demonstrating that it is safe and well-tolerated in healthy volunteers and in a number of conditions.
A Phase 2 clinical trial (NCT02160730) is currently recruiting an estimated 16 Cushing’s disease patients in the U.S., to test the safety and effectiveness over a four-week period. The effect of Seliciclib will be measured by a reduction in ACTH present in the blood, and a reduction in free cortisol in the urine to normal levels. The patients will be monitored for any adverse events throughout the trial.
The trial is being carried out in collaboration with clinicians at the Cedars Sinai Medical Center and is sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The first Cushing’s disease patient was treated with Seliciclib in this trial in 2015, and the estimated completion date of the trial is June 2019.
Seliciclib is administered orally. Previous clinical trials have demonstrated that Seliciclib may cause adverse effects, including nausea, vomiting, fatigue, hypokalemia (low potassium in the blood), and liver enzymes elevation.
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