Pasireotide (SOM230): development, mechanism of action and potential applications

Mol Cell Endocrinol. 2008 May 14;286(1-2):69-74. doi: 10.1016/j.mce.2007.09.006. Epub 2007 Sep 19.

Abstract

Pasireotide (SOM230) is a multi-receptor ligand somatostatin analogue with high binding affinity for somatostatin receptor subtypes sst(1,2,3) and sst(5). Pasireotide potently suppresses GH, IGF-I and ACTH secretion, indicating potential efficacy in acromegaly and Cushing's disease. The prolonged inhibition of hormone secretion by pasireotide in animal models and expression of multiple sst receptors in carcinoid tumors suggests that pasireotide may have clinical advantages over octreotide in patients with carcinoid tumors. Direct and indirect antitumor activity has been observed in vitro with pasireotide, including sst receptor-mediated apoptosis and antiangiogenesis, suggesting a possible role for pasireotide in antineoplastic therapy. In summary, preclinical evidence, as well as preliminary results from clinical studies suggests that pasireotide is a promising new treatment for patients with symptoms of metastatic carcinoid tumors refractory or resistant to octreotide, de novo or persistent acromegaly, and that pasireotide has the potential to be the first directed medical therapy for Cushing's disease.

Publication types

  • Review

MeSH terms

  • Acromegaly / drug therapy
  • Adrenocorticotropic Hormone / antagonists & inhibitors
  • Adrenocorticotropic Hormone / metabolism
  • Animals
  • Antineoplastic Agents, Hormonal / chemistry
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Carcinoid Tumor / drug therapy
  • Carcinoid Tumor / metabolism
  • Drug Resistance, Neoplasm
  • Growth Hormone / antagonists & inhibitors
  • Growth Hormone / metabolism
  • Humans
  • Insulin-Like Growth Factor I / antagonists & inhibitors
  • Insulin-Like Growth Factor I / metabolism
  • Octreotide / therapeutic use
  • Pituitary ACTH Hypersecretion / drug therapy
  • Receptors, Somatostatin / antagonists & inhibitors
  • Receptors, Somatostatin / biosynthesis*
  • Somatostatin / analogs & derivatives*
  • Somatostatin / chemistry
  • Somatostatin / therapeutic use
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Hormonal
  • Receptors, Somatostatin
  • Somatostatin
  • Insulin-Like Growth Factor I
  • Adrenocorticotropic Hormone
  • Growth Hormone
  • pasireotide
  • Octreotide