Pasireotide is a synthetic long-acting cyclic hexapeptide with somatostatin-like activity. It is marketed as a diaspartate salt called Signifor, indicated for the treatment of adult patients with Cushing’s disease for whom pituitary surgery is not an option or has not been curative. SIGNIFOR is an injectable cyclohexapeptide somatostatin analogue. Pasireotide exerts its pharmacological activity via binding to somatostatin receptors (ssts). Pasireotide binds and activates the hsst receptors resulting in inhibition of ACTH secretion, which leads to decreased cortisol secretion.

Somatostatin (also known as growth hormone-inhibiting hormone) is a naturally-occurring peptide hormone that regulates the endocrine system. Somatostatin is produced in gastrointestinal (GI) tract, pancreas, hypothalamus, and central nervous system (CNS) and some other organs. Somatostatin is initially secreted as a 116 amino acid precursor, preprosomatostatin, which undergoes endoproteolytic cleavage to prosomastatin. Prosomastatin is further process into two active forms, shorter isoform somatostatin-14 works primarily in the brain, while the longer somatostatin-28 (SST-28) form operates in the GI tract. Somatostatin produces predominantly neuroendocrine inhibitory effects across multiple systems. It is known to inhibit GI, endocrine, exocrine, pancreatic, and pituitary secretions, as well as modify neurotransmission and memory formation in the CNS. Somatostatin binds to six different receptors in various systems and cells throughout the body to produce its regulatory effect. These receptors are specific to somatostatin and classify as G-protein coupled receptors (GPCR). Somatostatin half-life is between 1 to 3 minutes. Due to its short half-life, somatostatin has been formulated exogenously in much more stable forms with a longer half-life; this allows for its primary clinical use, which is the treatment of neuroendocrine tumors.