| First Author | Yang S | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 43 | Pages | 17534-9 |
| PubMed ID | 24082113 | Mgi Jnum | J:201997 |
| Mgi Id | MGI:5516404 | Doi | 10.1073/pnas.1306285110 |
| Citation | Yang S, et al. (2013) Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models. Proc Natl Acad Sci U S A 110(43):17534-9 |
| abstractText | Loss-of-function mutations in the human voltage-gated sodium channel NaV1.7 result in a congenital indifference to pain. Selective inhibitors of NaV1.7 are therefore likely to be powerful analgesics for treating a broad range of pain conditions. Herein we describe the identification of micro-SLPTX-Ssm6a, a unique 46-residue peptide from centipede venom that potently inhibits NaV1.7 with an IC50 of approximately 25 nM. micro-SLPTX-Ssm6a has more than 150-fold selectivity for NaV1.7 over all other human NaV subtypes, with the exception of NaV1.2, for which the selectivity is 32-fold. micro-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. micro-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 micro-SPTX-Ssm6a as a promising lead molecule for the development of novel analgesics targeting NaV1.7, which might be suitable for treating a wide range of human pain pathologies. |
