Endothelin Receptor Antagonists

Abstract

Three pathways have been identified in the pathogenesis of pulmonary arterial hypertension (PAH): the endothelin (ET), nitric oxide (NO) and prostacyclin pathways. These pathways represent the targets of approved PAH therapies and their discovery has facilitated significant progress in the understanding and treatment of PAH. The ET system is well established as a key player in the pathophysiology of PAH, with deleterious effects mediated by both the ETA and ETB receptors. Endothelin receptor antagonists (ERAs) are an important part of PAH therapy, with two ERAs currently approved for the treatment of PAH and a novel ERA that has recently been investigated in a Phase III clinical trial. This chapter describes the role of ET in the pathogenesis of PAH, reviews experimental data and examines the clinical status of ERAs in PAH treatment.

Endothelin Receptor Antagonists: Status Quo and Future Perspectives for Targeted Therapy

“…Bosentan [20] Ambrisentan [21] Macitentan [22] Sitaxsentan [23] Atrasentan [24] Clazosentan [17] Zibotentan [25] Aprocitentan [26] Approval Bosentan is a non-peptide pyrimidine derivative that acts as a competitive, specific antagonist for both ET A and ET B . It was the first ERA to be approved for the treatment of PAH in patients with a World Health Organization (WHO) functional class III-IV [33].…”

Expression of the Endothelin-1 Gene and Its Type a Receptor including Physical Activity among Patients with Acute Myocardial Infarction

“…The stimulation of the ENDRA as a result of the action of endothelin-1 in smooth muscle cells increases the binding of proteoglycans with LDL particles, contributing to the development of hypercholesterolemia. Published research results suggest that blocking the endothelin receptor A affects endothelial-dependent vascular relaxation as a result of the increased availability of nitric oxide [ 22 ]. It also inhibits the progression of atherosclerotic lesions by limiting the formation of macrophages and oxidized LDL particles and the infiltration of monocytes.…”

Optimal conditions for the high yield of bioactive asterric acid from marine derived Fungus Aspergillus sp.

“…we had isolated a minor diphenyl secondary metabolite; asterric acid (figure 1). Asterric acid and its analogues have several interesting bioactivities like antifungal, antimicrobial, cytotoxic, fungicidal, pesticidal, nematicidal, seed germination inhibition ( LiuOptimal conditions for the high yield of bioactive asterric acid from marine derived … __________________________________________________________________________________________ __________________________________________________________________________________________ Natural and Applied Sciences International Journal (NASIJ) Lai et al, 2012;Liu et al, 2006;, anti-HIV activity (Hu et al, 2012), as a first non-peptide for endothelin binding inhibition (Ohashi et al, 1992;Ogawa et al, 1995), anti-plasmodial activity against the erythrocyte stages of chloroquine resistant Plasmodium falciparum (Talontsi et al, 2014), α-glucosidase inhibitory activities (Wang et al, 2016;Zhang et al, 2016), having vascular endothelial growth factor inhibitory activity (Lee et al, 2002) and as medicine for the initial stage of endothelin receptor agonist (Clozel et al, 2007). In this study, the yield of asterric acid is improved to multi gram quantity, through media optimization.…”