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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Aug 16;91(17):8052–8056. doi: 10.1073/pnas.91.17.8052

SB 209670, a rationally designed potent nonpeptide endothelin receptor antagonist.

E H Ohlstein 1, P Nambi 1, S A Douglas 1, R M Edwards 1, M Gellai 1, A Lago 1, J D Leber 1, R D Cousins 1, A Gao 1, J S Frazee 1, et al.
PMCID: PMC44543  PMID: 8058755

Abstract

An extremely potent and highly specific non-peptide, subnanomolar endothelin (ET) receptor antagonist, SB 209670, has been synthesized and characterized. SB 209670, which was rationally designed using conformational models of ET-1, selectively inhibits binding of 125I-labeled ET-1 to cloned human ET receptor subtypes ETA and ETB (Ki = 0.2 and 18 nM, respectively). SB 209670 produces concentration-dependent inhibition of ET-1-mediated vasoconstriction in isolated vascular tissues and in vivo following either intravenous or intraduodenal administration. SB 209670 produces a dose-dependent reduction in blood pressure in hypertensive rats, protects from ischemia-induced neuronal degeneration in a gerbil stroke model, and attenuates neointima formation following rat carotid artery balloon angioplasty. SB 209670 will be useful in characterizing and classifying the physiological and pathophysiological effects of ET.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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