Octreotide (acetate)

Octreotide is an octapeptide analog of somatostatin that binds to somatostatin receptors (SSTRs) with a higher affinity for the somatostatin subgroup 2 receptors, SST₂, SST₃, and SST₅ (K_is = 875, 0.57, 26.8, >1,000, and 6.8 nM for SST_1-5 receptors, respectively).¹ Within subgroup 2 SSTRs, it selectively binds to SST₂ over SST₃ and SST₅ receptors with IC₅₀ values of 0.02, 92.9, and 21.8 nM, respectively, for human receptors. Octreotide inhibits the secretion of growth hormone in vitro in rat pituitary cells three-fold more potently than somatostatin and in vivo in rhesus monkey (ID₅₀ = 0.38 μg/kg per hour).² It inhibits proliferation of VEGF-stimulated human umbilical endothelial cells (HUVECs) with an EC₅₀ value of approximately 1 μM.³ It also inhibits growth of LCI-D20 human hepatocellular carcinoma cell tumors in a nude mouse xenograft model when administered at a dose of 50 μg/kg twice daily. Formulations containing octreotide have been used in the treatment of acromegaly to reduce growth hormone and IGF-1 levels.

1. Moore, S.B., van der Hoek, J., de Capua, A., et al. Discovery of iodinated somatostatin analogues selective for hsst2 and hsst5 with excellent inhibition of growth hormone and prolactin release from rat pituitary cells J. Med. Chem. 48(21),6643-6652(2005).
2. Bauer, W., Briner, U., Doepfner, W., et al. SMS 201-995: A very potent and selective octapeptide analogue of somatostatin with prolonged action Life Sci. 31(11),1133-1140(1982).
3. Jia, W.-D., Xu, G.-L., Xu, R.-N., et al. Octreotide acts as an antitumor angiogenesis compound and suppresses tumor growth in nude mice bearing human hepatocellular carcinoma xenografts J. Cancer Res. Clin. Oncol. 129(6),327-334(2003).