Sitaxsentan

Sitaxsentan (IPI 1040 sodium; TBC11251 sodium) is a potent, selective and orally active endothelin A receptor (ETA) antagonist with an IC₅₀ of 1.4 nM and a K_i of 0.43 nM. Sitaxsentan exhibits an IC₅₀ for the ETB receptor of as high as 9800 nM. Sitaxsentan is metabolized by CYP2C9 and CYP3A4, normalizes shunt-induced endothelial abnormalities, restores BMPR signaling, and suppresses pulmonary vascular remodeling and hemodynamic deterioration. Sitaxsentan can be applied in the research of pulmonary arterial hypertension and portopulmonary hypertension^{[1][2][3][4][5]}. In Vitro:Sitaxsentan (100 μM, 10 min) significantly inhibits taurocholate cotransporter (NTCP) and organic anion transporter (OATP) transportation in sandwich-cultured human hepatocytes^[3].
Sitaxsentan (10 min) has a high efficiency of liver cell uptake and almost no bile excretion^[3].
Sitaxsentan has moderate hepatobiliary transporters bile salt export pump (BSEP) inhibition (IC₅₀ = 25 μM) in sandwich-cultured human hepatocytes^[5].
In Vivo:Sitaxsentan (1.5 mg/kg, p.o., three times a day for 3 months) effectively prevents PAH caused by shunt induction, and the combined medication with Sildenafil (HY-15025) has a better effect in piglets^[1].
Sitaxsentan (5 mg/kg, i.v., single dose) completely blocks the activation of ETA receptors in the acute hypoxia model of rats^[2].
Sitaxsentan (15-30 mg/kg, p.o., once daily for 2-4 weeks) significantly improves PAH and vascular remodeling caused by chronic hypoxia, but has limited effect on the already formed right ventricular hypertrophy in rat chronic hypoxia model^[2].
Sitaxsentan (10-50 mg/kg, p.o., once daily for 3 weeks) dose-dependently improves Monocrotaline(HY-N0750)-induced pulmonary hypertension in rats^[2].