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Discovery of a selective Na(V)1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models
文献类型：期刊论文
| 作者 | Yang SL1,2; Xiao Y1,2; Kang D1,2; Liu J1,2; Li Y1,2; Undheim EAB3; Klint JK3; Rong MQ[*]1; Lai R[*]1; King GF[*]3 |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2013 |
| 卷号 | 110期号:43页码:17534-17539 |
| 关键词 | chronic pain drug discovery peptide therapeutic |
| 通讯作者 | rongmingqiang@mail.kiz.ac.cn ; rlai@mail.kiz.ac.cn ; glenn.king@imb.uq.edu.au |
| 合作状况 | 其它 |
| 英文摘要 | Loss-of-function mutations in the human voltage-gated sodium channel Na(V)1.7 result in a congenital indifference to pain. Selective inhibitors of Na(V)1.7 are therefore likely to be powerful analgesics for treating a broad range of pain conditions. Herein we describe the identification of mu-SLPTX-Ssm6a, a unique 46-residue peptide from centipede venom that potently inhibits Na(V)1.7 with an IC50 of similar to 25 nM. mu-SLPTX-Ssm6a has more than 150-fold selectivity for Na(V)1.7 over all other human Na-V subtypes, with the exception of Na(V)1.2, for which the selectivity is 32-fold. mu-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. mu-SLPTX-Ssm6a proved to be a more potent analgesic than morphine in a rodent model of chemical-induced pain, and it was equipotent with morphine in rodent models of thermal and acid-induced pain. This study establishes mu-SPTX-Ssm6a as a promising lead molecule for the development of novel analgesics targeting Na(V)1.7, which might be suitable for treating a wide range of human pain pathologies. |
| 收录类别 | SCI |
| 资助信息 | This study was supported by the Chinese Na- tional Natural Science Foundation (30830021, 31025025, 31070701, 31000960, 31025025, U1132601, 31200590), the Chinese Ministry of Science and Technology (2010CB529800,2011ZX09102-002-10),YunnanProvince(2011CI139,2012BC009), and the Australian Research Council (Discovery Grant DP110103129). |
| 语种 | 英语 |
| WOS记录号 | WOS:000325943300078 |
| 公开日期 | 2013-11-25 |
| 源URL | [http://159.226.149.42:8088/handle/152453/7709]  |
| 专题 | 昆明动物研究所_动物毒素室 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences and Yunnan Province, Kunming 650223, Yunnan, China 2.Graduate School of Chinese Academy of Sciences, Beijing 100009, China 3.c Division of Chemistry and Structural Biology, Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia |
| 推荐引用方式 GB/T 7714 | Yang SL,Xiao Y,Kang D,et al. Discovery of a selective Na(V)1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2013,110(43):17534-17539. |
| APA | Yang SL.,Xiao Y.,Kang D.,Liu J.,Li Y.,...&King GF[*].(2013).Discovery of a selective Na(V)1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,110(43),17534-17539. |
| MLA | Yang SL,et al."Discovery of a selective Na(V)1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 110.43(2013):17534-17539. |
入库方式： OAI收割
来源：昆明动物研究所
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