Pasireotide (diaspartate)

Pasireotide (SOM230) diaspartate, a long-acting cyclohexapeptide somatostatin analogue, can improve agonist activity at somatostatin receptors (subtypes sst1/2/3/4/5, pKi=8.2/9.0/9.1/<7.0/9.9, respectively). Pasireotide diaspartate exhibits antisecretory, antiproliferative, and proapoptotic activity[1][2].

Research Areas >> Cancer

Signaling Pathways >> GPCR/G Protein >> Somatostatin Receptor

Research Areas >> Neurological Disease

pKi: 8.2 (sst1), 9.0 (sst2), 9.1 (sst3), <7.0 (sst4), 9.9 (sst5)[1]

Pasireotide diaspartate exhibits unique high-affinity binding to human somatostatin receptors (subtypes sst1/2/3/4/5, pKi=8.2/9.0/9.1/<7.0/9.9, respectively)[1]. Pasireotide diaspartate effectively inhibits the growth hormone releasing hormone (GHRH) induced growth hormone (GH) release in primary cultures of rat pituitary cells, with an IC50 of 0.4 nM[1].

Pasireotide (160 mg/kg/mouth; s.c. for 4 months) diaspartate significantly decreases the serum insulin, increases serum glucose, reduces the tumor size and increases apoptosis in Pdx1-Cre[2]. Pasireotide (2-50 μg/kg; s.c. twice daily for 42 days) diaspartate exerts the antinociceptive and antiinflammatory actions via the SSTR2 receptor in a mouse model of immune-mediated arthritis[3]. Animal Model: 12 month-old conditional Men1 knockout mice with insulinoma[2] Dosage: 160 mg/kg/mouth Administration: S.c. every month for 4 months Result: Decreased the serum insulin from 1.060 μg/L to 0.3653 μg/L and increased the serum glucose from 4.246 mM to 7.122 mM. Significantly reduced the tumor size and increased apoptosis.

[1]. Lewis I, et, al. A novel somatostatin mimic with broad somatotropin release inhibitory factor receptor binding and superior therapeutic potential. J Med Chem. 2003 Jun 5;46(12):2334-44.

[2]. Quinn TJ, et, al. Pasireotide (SOM230) is effective for the treatment of pancreatic neuroendocrine tumors (PNETs) in a multiple endocrine neoplasia type 1 (MEN1) conditional knockout mouse model. Surgery. 2012 Dec;152(6):1068-77.

[3]. Imhof AK, et, al. Differential antiinflammatory and antinociceptive effects of the somatostatin analogs octreotide and pasireotide in a mouse model of immune-mediated arthritis. Arthritis Rheum. 2011 Aug;63(8):2352-62.