Endothelin A receptors

G Protein-Coupled Receptors (GPCRs) ttiA Adrenergic Receptor Dopamine D3 Receptor Endothelin A Receptor... 

Astles PC, Brown TJ, Handscombe CM, Harper MF, Harris NV, Lewis RA, Lockey PM, McCarthy C, McLay IM, Porter B, Roach AG, Smith C, Walsh RJA. Selective endothelin A receptor antagonists. 1. Discovery and structure-activity of 2,4-disubstituted benzoic acid derivatives. Eur J Med Ghent 1997 32 409-23. 

Endothelin-1, one of the most potent physiologic vasoconstrictors, is an important contributor to HF pathophysiology.9 Endothelin-1 binds to two G-protein coupled receptors, endothelin-A (ET-A) and endothelin-B (ET-B). Endothelin-A receptors mediate vasoconstriction and are prevalent in vascular smooth muscle and cardiac cells. Endothelin-B receptors are expressed on the endothelium and in vascular smooth muscle, and receptor stimulation mediates vasodilation. Levels of ET-1 correlate with HF functional class and mortality. 

Murugesan N, Gu Z, Fadnis L, et al. Dual angiotensin II and endothelin A receptor antagonists synthesis of 2 -substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokinetics. J Med Chem 2005 48 171-179. 

Telgmann, R., Harb, B. A., Ozcelik, C., et al. (2007) The G-231A polymorphism in the endothelin-A receptor gene is associated with lower aortic pressure in patients with dilated cardiomyopathy. Am. J. Hypertens. 20, 32-37. 

Endothelin-A receptor antagonist BQ-610 blocks cigarette smoke-induced mitogenesis in rat airways and vessels. 

Kling A, Muller S, Raschack M, Unger L, Walker N, Wemet W. Discovery and optimization of a novel class of orally active non-peptidic endothelin-A receptor antagonists./. Med. Chem., 1996, 39, 2123-2128. 

Rivaroxaban (BAY 59-7939) <2005JME5900> is an oral anticoagulant currently under development. It acts by inhibiting the active form of coagulation factor Xa. Sitaxentan <2004JME1969, 2005MI985> is an orally active sulfonamide class endothelin-A receptor antagonist. 

Bosentan is an endothehn-A and endothehn-B receptor antagonist. It is effective in pulmonary arterial hjrpertension (1,2) and has been marketed for this indication. The studies showed an improvement in exercise capacity and dyspnea and an increased time to clinical worsening. Efficacy in pulmonary hjrpertension has also been reported in an open study with a selective endothelin-A receptor antagonist (3). 

Barst RJ, Rich S, Widlitz A, Horn EM, McLaughlin V, McFarhn J. Clinical efficacy of sitaxsentan, an endothelin-A receptor antagonist, in patients with pulmonary arterial hypertension open-label pilot study. Chest 2002 121(6) 1860-8. 

Flunley TE, Fogo A, Iwasaki S, Kon V. Endothelin A receptor mediates functional but not structural damage in chronic cyclosporine nephrotoxicity. J Am Soc Nephrol 1995 5 1718-1723. 

A.T. Gonon, A.V. Gourine, R.J.M. Middelveld, K. Alving and J. Pemow, Limitation of infarct size and attenuation of myeloperoxidase activity by an endothelin A receptor antagonist following ischemia and reperfusion, Bas. Res. Cardiol. 96, 454-462 (2001). 

Several experimental systems to check the inhibition potency of bile add transport have been characterized. Using sandwich-cultured human hepatocytes, bosentan, cyclosporin A, CI-1034 (endothelin-A receptor antagonist), glyburide, erythromycin estolate, and troleandomycin could inhibit the taurocholate efflux to the bile pocket [234]. Moreover, Mita et al. [235] construded NTCP/BSEP double-transfeded cells and some cholestasis-induced compounds inhibited both the NTCP-mediated uptake and the BSEP-mediated efflux of taurocholate. Then, they have found fluorescent bile acids whose transcellular transport was dearly observed, which may be used for the rapid identification of inhibitors of NTCP and BSEP in drug screening process [235]. 

Barst RJ, Langleben D, Badesch D, et al STRIDE-2 Study Group. Treatment of pulmonary arterial hypertension with the selective endothelin-A receptor antagonist sitaxsentan. J Am Coll Cardiol 2006 47(10) 2049-56. 

Clouthier, D.E., Hosoda, K., Richardson, J.A., Williams, S.C., Yanagisawa, H., Kuwaki, T., Kumada, M., Hammer, R.E., Yanagisawa, M. 1998. Cranial and cardiac neural crest defects in endothelin-A receptor-deficient mice. Development 125, 813-824. 

M., Chin, M., and Sills, M. A. (1993) Isolation and structure elucidation of 34-sulfatobastadin 13, an inhibitor of the endothelin A receptor, from a marine sponge of the genus lanthella. J Nat Prod. 56,1613-1617. 

Synthesis and solution conformation of c(D-Trp-D-Cys(S03-Na ")-Pro-D-Val-Leu), a potent endothelin-A receptor antagonist. Int. 

Riechers, H., Albrecht, H.-P, Aberg, W., Baumann, E., Bernard, H., Bohm, H.-J., Klinge, D., Kling, A., Muller, S., Raschack, M., Unger, L., Walker, N., Wernet, W. Discovery and optimization of a novel class of orally active nonpeptidic Endothelin-A receptor antagonists. J. Med. Chem. 1996, 39, 2123-2128. 

Doherty, A. M., and Uprichard, A. C. (1998). Discovery and development of an endothelin A receptor-selective antagonist PD 156707. Pharm Biotechnol 11, 81-112. 

McDuffie, J. E., Yu, X., Sobocinski, G., Song, Y, Chupka, J., and Albassam, M. (2006). Acute coronary artery injury in dogs following administration of Cl-1034, an endothelin A receptor antagonist. Cardiovasc Toxicol 6, 25-38. 

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