Biological Activity
prx-08066 is a selective antagonist of 5-hydroxytryptamine receptor 2b (5-ht2br) with ki value of 3.4nm [1].prx-08066 is found to causes selective vasodilation of pulmonary arteries and is developed to treat for pulmonary arterial hypertension (pah). in the in vitro studies, prx-08066 shows effects on the vascular muscularization induced by 5-ht. it inhibits 5-ht induced mitogen-activated protein kinase activation with ic50 value of 12nm. in addition, it significantly reduces thymidine incorporation in cho cells expressing human 5-ht2br with ic50 value of 3nm. in both mice and rat models, prx-08066 reverses the hypoxia-dependent increase in right ventricular systolic pressure. besides that, prx-08066 is also found to have anti-proliferative and anti-fibrotic effects. it inhibits the secretion of 5-ht, the phosphorylation of erk1/2 and synthesis of profibrotic growth factor. moreover, prx-08066 inhibits the proliferation of the small intestinal neuroendocrine tumor cell line krj-i with ic50 value of 4.6nm [1, 2].
References
[1] porvasnik s l, germain s, embury j, et al. prx-08066, a novel 5-hydroxytryptamine receptor 2b antagonist, reduces monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rats. journal of pharmacology and experimental therapeutics, 2010, 334(2): 364-372.
[2] svejda b, kidd m, giovinazzo f, et al. the 5-ht2b receptor plays a key regulatory role in both neuroendocrine tumor cell proliferation and the modulation of the fibroblast component of the neoplastic microenvironment. cancer, 2010, 116(12): 2902-2912.
