Pasireotide (aspartate) (trifluoroacetate salt)

Pasireotide is a somatostatin receptor (SSTR) agonist that binds selectively to SST₁, SST₂, SST₃, and SST₅ over SST₄ (IC₅₀s = 9.3, 1, 1.5, 0.16, and >100 nM, respectively, for human recombinant receptors).¹ It dose-dependently inhibits growth hormone release stimulated by growth hormone-releasing hormone (GHRH) in primary rat anterior pituitary cells and inhibits adrenocorticotropic hormone (ACTH) secretion by some primary human corticotrope adenomas at a concentration of 10 nM.^1,2 Pasireotide (10 nM) also inhibits ACTH release from and proliferation of mouse AtT20 pituitary corticotrope cells in vitro and inhibits tumor growth of subcutaneously implanted AtT20 cells in vivo in nude mice when administered at a dose of 1.5 μg per day.³ Pasireotide (0.03 mg/kg) decreases plasma ACTH concentrations and tumor size in dogs with ACTH-dependent Cushing's disease.⁴ Formulations containing pasireotide have been used in the treatment of acromegaly and Cushing's disease.

1.Bruns, C., Lewis, I., Briner, U., et al.SOM230: a novel somatostatin peptidomimetic with broad somatotropin release inhibiting factor (SRIF) receptor binding and a unique antisecretory profileEur. J. Endocrinol.146(5)707-716(2002) 2.Hofland, L.J., van der Hoek, J., Feelders, R., et al.The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5Eur. J. Endocrinol.152(4)645-654(2005) 3.Murasawa, S., Kageyama, K., Sugiyama, A., et al.Inhibitory effects of SOM230 on adrenocorticotropic hormone production and corticotroph tumor cell proliferation in vitro and in vivoMol. Cell. Endocrinol.394(1-2)37-46(2014) 4.Castillo, V., Theodoropoulou, M., Stalla, J., et al.Effect of SOM230 (pasireotide) on corticotropic cells: Action in dogs with Cushing's diseaseNeuroendocrinology94(2)124-136(2011)