Discovery of a selective Na_V1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models

Yang S.; Xiao Y.; Kang D.Liu J.Li Y.Undheim E.A.B.Klint J.K.Rong M.Lai R.King G.F.

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Discovery of a selective Na_V1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models

【24h】

Discovery of a selective Na_V1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models

机译：Discovery of a selective Na_V1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相关主题

摘要

Loss-of-function mutations in the human voltage-gated sodium channel Na_V1.7 result in a congenital indifference to pain. Selective inhibitors of Na_V1.7 are therefore likely to be powerful analgesics for treating a broad range of pain conditions. Herein we describe the identification of μ-SLPTX-Ssm6a, a unique 46-residue peptide from centipede venom that potently inhibits Na_V1.7 with an IC_(50) of ～25 nM. μ-SLPTX-Ssm6a has more than 150-fold selectivity for Na _V1.7 over all other human Na_V subtypes, with the exception of Na_V1.2, for which the selectivity is 32-fold. μ-SLPTX-Ssm6a contains three disulfide bonds with a unique connectivity pattern, and it has no significant sequence homology with any previously characterized peptide or protein. μ-SLPTX-Ssm6a proved to be a more potent analgesic than morphine in a rodent model of chemicalinduced pain, and it was equipotent with morphine in rodent models of thermal and acid-induced pain. This study establishes μ-SPTX-Ssm6a as a promising lead molecule for the development of novel analgesics targeting Na_V1.7, which might be suitable for treating a wide range of human pain pathologies.

著录项

来源
《Proceedings of the National Academy of Sciences of the United States of America》 |2013年第43期|17534-17539|共6页
作者
Yang S.; Xiao Y.; Kang D.Liu J.Li Y.Undheim E.A.B.Klint J.K.Rong M.Lai R.King G.F.;
展开▼
作者单位

Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences and Yunnan Province, Kunming 650223, Yunnan, China;

Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia;

展开▼
收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Chronic pain; Drug discovery; Peptide therapeutic;

Discovery of a selective Na_V1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models

摘要

著录项

相关主题

期刊订阅