EDNRA binds selective ERAs

Stable Identifier
R-HSA-9731931
Type
Reaction [binding]
Species
Homo sapiens
Compartment
Synonyms
EDNRA binds selective EDNR antagonists
ReviewStatus
5/5
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Endothelins (EDNs) are 21-amino acid vasoconstricting peptides produced primarily in the endothelium that play a key role in vascular homeostasis. They are potent and long-lasting vasoconstrictors. An imbalance and over-expression of EDNs can contribute to hypertension (high blood pressure). EDNs bind to two endothelin receptors, EDNRA and EDNRB. EDNRA is primarily located in the smooth muscle of blood vessels and upon EDN binding, leads to vasoconstriction and sodium retention, ultimately increasing blood pressure. EDNRB is primarily located on endothelial cells lining the internal walls of vasculature. EDN binding to EDNRB leads to the release of NO (nitric oxide), a powerful vasodilator.

EDNR antagonists (ERAs) are competitive antagonists of EDNs at EDNRs. ERAs selective for EDNRA are primarily indicated for pulmonary arterial hypertension (PAH) (Zheng et al. 2020). EDNRA-selective approved drugs are sitaxentan (Wu et al. 1997) and ambrisentan (Bolli et al. 2004).

Ambrisentan has been shown to inhibit cancer cell migration, invasion and metastasis in vitro, suggesting a new therapeutic application for this drug (Kappes et al. 2020).
Literature References
PubMed ID Title Journal Year
9171878 Discovery of TBC11251, a potent, long acting, orally active endothelin receptor-A selective antagonist

Okun, I, Chan, MF, Keller, KM, Dixon, RA, Raju, B, Stavros, F, Kogan, TP, Mong, S, Wu, C, Brock, T

J Med Chem 1997
15139756 Novel benzo[1,4]diazepin-2-one derivatives as endothelin receptor antagonists

Marfurt, J, Grisostomi, C, Fischli, W, Treiber, A, Ramuz, H, Bur, D, Morrison, K, Clozel, M, Hess, P, Weller, T, Binkert, C, Thorin, E, Bolli, MH, Buchmann, S, Boss, C

J Med Chem 2004
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