PRX-08066 (maleate)

PRX-08066 maleate is a selective and orally active 5-hydroxytryptamine receptor 2B (5-HT2BR) antagonist with a K_i of 3.4 nM. PRX-08066 maleate inhibits the MAPK pathway, 5-HT release and fibrotic factor (TGFβ1, CTGF and FGF2) expression. PRX-08066 maleate inhibits the proliferation of KRJ-I cells and induces apoptosis (caspase-3 activation). PRX-08066 maleate inhibits pulmonary vascular remodeling. PRX-08066 maleate can be used of pulmonary Arterial Hypertension (PAH) and neuroendocrine tumor (NET)^[1][2]. IC50 & Target:IC50 value: 3.4 nM [1] In Vitro:PRX-08066 maleate inhibits 5-HT induced mitogen-activated protein kinase activation (IC₅₀ = 12 nM) and markedly reduced thymidine incorporation (IC₅₀ = 3 nM) in hamster ovary cells expressing the human 5-HT2BR^[1].
. PRX-08066 (0.01 pM-100 pM, 24 h) maleate significantly inhibits the proliferation of KRJ-I cells with an IC₅₀ of 4.6 pM and has no significant effect on NCI-H720 cells (with no expression of 5-HT2B receptors)^[2].
PRX-08066 (0.01 pM-100 pM) maleate inhibits basal and Isoproterenol (HY-B0468)-stimulated 5-HT secretion with IC₅₀s of 6.9 pM and 1.25 pM in KRJ-I cells^[2].
PRX-08066 (0.5 pM) maleate significantly reduces the phosphorylation level of ERK in KRJ-I cells^[2].
PRX-08066 (1-2 h) maleate reduces fibrotic factors (TGFβ1, CTGF, FGF2) in KRJ-I cells^[2].
PRX-08066 (1 pM, 24 h) maleate significantly increases the proportion of apoptotic cells by activating Caspase-3 in KRJ-I cells and HEK293 cells established in a coculture system^[2].
In Vivo:PRX-08066 (50-100 mg/kg, p.o., twice daily for 5 weeks) maleate improves pulmonary vascular remodeling, right ventricular hypertrophy and cardiac function in Monocrotaline (MCT) (HY-N0750)-induced PAH rats^[1].