Nebentan (YM598) is a potent, selective and orally active non-peptide endothelin ETA receptor antagonist through the modification of Bosentan . Nebentan inhibits [125I] endothelin-1 binding to cloned human endothelin ETA and ETB receptor, with Ki of 0.697 nM and 569 nM, respectively[1]. YM598 can ameliorate the progression of cor pulmonale and myocardial infarction in vivo[2].

ETB:569 nM (Ki), ETA:0.697 nM (Ki)

Nebentan inhibits the specific binding of [125I] endothelin-1 to endothelin ETA and ETB receptors in a concentration-dependent manner, with Ki values of 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 ETB receptors, with Ki values of 569 nM and 155 nM, respectively [1]. Nebentan also inhibits the endothelin-1-induced increase in intracellular Ca2+ concentration ([Ca2+]i) in both CHO and A10 cells, with IC50 values of 26.2 nM and 26.7 nM, respectively [1].

Nebentan, administered orally at dosages of 0.1-1 mg/kg for 4 weeks, significantly impedes the advancement of pulmonary hypertension and the formation of right ventricular hypertrophy. Additionally, when administered at a dosage of 1 mg/kg over 30 weeks, it markedly improves the survival rates of CHF rats, significantly reducing the hypertrophy of both ventricles and alleviating pulmonary congestion.