Vapreotide acetate

Biological Activity

Vapreotide acetate (BMY-41606 acetate; RC160 acetate) is a neurokinin-1 (NK1) receptor antagonist with IC50 value of 330 nM. Vapreotide inhibits SP-induced IL-8 and MCP-1 production in HEK293-NK1R and U373MG cell lines. Vapreotide also inhibits HIV-1 infection of human MDM in vitro, an effect that is reversible by SP pretreatment. Vapreotide inhibits serum-induced proliferation of CHO cells expressing SSTR2 and SSTR5 with EC50 of 53 and 150 pM, respectively.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

Analog of somatostatin vapreotide exhibits biological effects in vitro via interaction with neurokinin-1 receptor
Sergei Spitsin, et al. Neuroimmunomodulation. 2013;20(5):247-55. PMID: 23921645.

Hemodynamic effects of acute and chronic administration of vapreotide in rats with cirrhosis
Nary Veal, et al. Dig Dis Sci. 2003 Jan;48(1):154-61. PMID: 12645803.

Relative potencies of the somatostatin analogs octreotide, BIM-23014, and RC-160 on the inhibition of hormone release by cultured human endocrine tumor cells and normal rat anterior pituitary cells
L J Hofland, et al. Endocrinology. 1994 Jan;134(1):301-6. PMID: 7903931.

Inhibition of cell proliferation by the somatostatin analogue RC-160 is mediated by somatostatin receptor subtypes SSTR2 and SSTR5 through different mechanisms
L Buscail, et al. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1580-4. PMID: 7878022.