DESCRIPTION PRX-08066 Maleic acid is a selective 5-HT2B receptor antagonist with IC50 value of 3.4 nM. (BOC Sciences Bioactive Compounds)

DESCRIPTION PRX 08066, a selective 5-hydroxytryptamine receptor 2B(5-HT2BR) antagonist, causes selective vasodilation of pulmonary arteries. Its IC50 value is 3.4 nM. It can potentially inhibit the pathologic 5-HT-induced vascular muscularization and is developed to treat for pulmonary arterial hypertension (PAH). It reduces monocrotaline-induced pulmonary arterial hypertension and right ventricular hypertrophy in rats. It shows effects on the vascular muscularization induced by 5-HT in the in vitro studies. It inhibits 5-HT-induced mitogen-activated protein kinase activation and markedly reduces thymidine incorporation in Chinese hamster ovary cells expressing the human 5-HT2BR in vitro. It decreases level of transcripts of TGFβ1, FGF2 and TPH1 in KRJ-I cells. It significantly reduces peak pulmonary artery pressure at 50 mg/kg and 100 mg/kg compared with monocrotaline control rats. It also significantly attenuates the elevation in pulmonary artery pressure and RV hypertrophy and maintains cardiac function. It reduces the hypoxia-dependent increase in right ventricular systolic pressure in both rats and mice without affecting the systemic mean arterial pressure in the animals. It is also found to have anti-proliferative and anti-fibrotic effects. It was developed by Allergan company and is in clinical phase 2 with no progression. (BOC Sciences Bioactive Compounds)