Vapreotide (acetate)

Vapreotide acetate (RC-160 acetate; BMY-41606 acetate) is a neurokinin-1 (NK1) receptor antagonist, with an IC₅₀ of 330 nM. In Vitro: Vapreotide attenuates the Substance P (SP)-triggered intracellular calcium increases and NF-κB activation in a dose-dependent manner. Vapreotide also inhibits SP-induced IL-8 and MCP-1 production in HEK293-NK1R and U373MG cell lines. Vapreotide inhibits HIV-1 infection of human MDM in vitro, an effect that is reversible by SP pretreatment^[1]. Vapreotide significantly inhibits GH-, PRL, and/or alpha-subunit release by human GH-secreting pituitary adenoma cells in concentrations as low as 10^-12-10^-14 M. Vapreotide inhibits GH release with an IC₅₀ of 0.1 pM^[2]. Vapreotide exhibits moderate-to-high affinities for SSTR2, -3, and -5 (IC₅₀=0.17, 0.1 and 21 nM, respectively) and low affinity for SSTR1 and -4 (IC₅₀=200 and 620 nM, respectively). RC-160 inhibits serum-induced proliferation of CHO cells expressing SSTR2 and SSTR5 (EC₅₀=53 and 150 pM, respectively)^[3]. In Vivo: In cirrhosis, bleeding by rupture of oesophagogastric varices is a severe complication of portal hypertension. The acute administration of vapreotide to rats decreases collateral circulation blood flow while chronic administration attenuated its development^[4]. Tumor volumes and weights are reduced by about 40% by RC-160 by s.c. injections at doses of 100 μg/day/animal. Vapreotide can inhibit the growth of androgen-independent prostate cancer when the therapy is started at an early stage of tumor development^[5].