Nebentan

Nebentan (YM598 free base) is a potent, selective and orally active non-peptide endothelin ET_A receptor antagonist through the modification of Bosentan (HY-A0013). Nebentan inhibits [¹²⁵I] endothelin-1 binding to cloned human endothelin ETA and ETB receptor, with K_i of 0.697 nM and 569 nM, respectively^[1]. YM598 can ameliorate the progression of cor pulmonale and myocardial infarction in vivo^[2]. In Vitro: Nebentan inhibits the specific binding of [¹²⁵I] endothelin-1 to endothelin ET_A and ET_B receptors in a concentration dependent manner, K_i values are 0.697 nM and 1.53 nM for human and rat endothelin ETA receptors, respectively. In contrast, YM598 exhibits low affinities for human and rat endothelin ET_B receptors, with K_i values of 569 nM and 155 nM,respectively^[1].
In measurement of intracellular Ca²⁺ concentration, Nebentan concentration-dependently inhibits the increase in [Ca²⁺]i induced by 10 nM endothelin-1 in both CHO cells and A10 cells, the IC₅₀ values are 26.2 nM for CHO cells and 26.7 nM for A10 cells, respectively^[1].
In Vivo: Nebentan (oral administration; 0.1-1 mg/kg; 4 weeks) significantly inhibits the progression of pulmonary hypertension and the development of right ventricular hypertrophy^[2].
Nebentan (oral administration; 1 mg/kg; 30 weeks) significantly ameliorates the poor survival rate of CHF rats, it markedly reduces the hypertrophy of both ventricles as well as pulmonary congestion^[2].