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SB 209670，一种经合理设计的强效非肽类内皮素受体拮抗剂。

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

作者信息

Ohlstein E H, Nambi P, Douglas S A, Edwards R M, Gellai M, Lago A, Leber J D, Cousins R D, Gao A, Frazee J S

机构信息

Department of Medicinal Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.

出版信息

Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):8052-6. doi: 10.1073/pnas.91.17.8052.

DOI:10.1073/pnas.91.17.8052
PMID:8058755
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC44543/
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.

摘要

一种效力极强且高度特异的非肽类、亚纳摩尔级内皮素（ET）受体拮抗剂SB 209670已被合成并进行了特性鉴定。SB 209670是利用ET-1的构象模型合理设计而成的，它能选择性抑制125I标记的ET-1与克隆的人类ET受体亚型ETA和ETB的结合（Ki分别为0.2和18 nM）。SB 209670在离体血管组织以及静脉或十二指肠给药后的体内实验中，对ET-1介导的血管收缩产生浓度依赖性抑制作用。SB 209670能使高血压大鼠的血压产生剂量依赖性降低，在沙鼠中风模型中可保护免受缺血诱导的神经元变性，并减轻大鼠颈动脉球囊血管成形术后的新内膜形成。SB 209670将有助于表征和分类ET的生理和病理生理效应。

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