Pasireotide--a somatostatin analog for the potential treatment of acromegaly, neuroendocrine tumors and Cushing's disease.
Pasireotide (SOM-230) is a small somatostatin (SST) analog that is being developed by Novartis Pharma AG for the potential treatment of acromegaly, Cushing's disease and neuroendocrine tumors; the compound is currently in phase III clinical trials for Cushing's disease. Pasireotide exhibits high binding affinity to four of the five human (h)SST receptor subtypes, with IC50 values for hSST5 > hSST2 > hSST3 > hSST1; the compound displays no affinity for hSST4. The affinity profile of pasireotide resembles the profile of endogenous SSTs--a feature that is favorable given that different tumors exhibit differing SST receptor expression profiles. Pasireotide also exhibits a longer half-life than the clinically available SST analogs octreotide or lanreotide. Thus, this compound may be a better therapeutic agent than other analogs. In phase II clinical trials, pasireotide inhibited growth hormone (GH) secretion from GH-secreting pituitary tumors, controlled symptoms associated with metastatic carcinoid tumors, and inhibited adrenocorticotropic hormone secretion in Cushing's disease. However, a major advantage for pasireotide compared with octreotide was not demonstrated. Commonly encountered side effects for the compound included mild to moderate gastrointestinal events (diarrhea, abdominal discomfort, nausea and vomiting). The efficacy of pasireotide and any potential advantage over current therapies will need to be tested or validated in larger phase III clinical trials.
Ben-Shlomo
Anat
A
Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048, USA.
Melmed
Shlomo
S
D000172:Acromegaly / Q000188:drug therapy*; D000818:Animals; D004353:Drug Evaluation, Preclinical; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D009842:Oligopeptides / Q000627:therapeutic use*; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy*; D013004:Somatostatin / Q000031:analogs & derivatives; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D019382:Human Growth Hormone; D013004:Somatostatin; C517782:pasireotide