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Proc Natl Acad Sci U S A
2013 Oct 22;11043:17534-9. doi: 10.1073/pnas.1306285110.
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Discovery of a selective NaV1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models.
Yang S
,
Xiao Y
,
Kang D
,
Liu J
,
Li Y
,
Undheim EA
,
Klint JK
,
Rong M
,
Lai R
,
King GF
.
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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 µ-SLPTX-Ssm6a, a unique 46-residue peptide from centipede venom that potently inhibits NaV1.7 with an IC50 of ∼25 nM. µ-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. 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 chemical-induced 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 NaV1.7, which might be suitable for treating a wide range of human pain pathologies.
Ahmad,
A stop codon mutation in SCN9A causes lack of pain sensation.
2007, Pubmed
Ahmad,
A stop codon mutation in SCN9A causes lack of pain sensation.
2007,
Pubmed
Basbaum,
Cellular and molecular mechanisms of pain.
2009,
Pubmed
Beacham,
Sites and molecular mechanisms of modulation of Na(v)1.2 channels by Fyn tyrosine kinase.
2007,
Pubmed
Black,
Expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to central preterminal branches and terminals in the dorsal horn.
2012,
Pubmed
Bosmans,
Deconstructing voltage sensor function and pharmacology in sodium channels.
2008,
Pubmed
,
Xenbase
Bosmans,
Four novel tarantula toxins as selective modulators of voltage-gated sodium channel subtypes.
2006,
Pubmed
,
Xenbase
Brennan,
Pain management: a fundamental human right.
2007,
Pubmed
Caldwell,
Sodium channel Na(v)1.6 is localized at nodes of ranvier, dendrites, and synapses.
2000,
Pubmed
Chen,
Expression and characterization of jingzhaotoxin-34, a novel neurotoxin from the venom of the tarantula Chilobrachys jingzhao.
2009,
Pubmed
Clare,
Targeting voltage-gated sodium channels for pain therapy.
2010,
Pubmed
Cox,
An SCN9A channelopathy causes congenital inability to experience pain.
2006,
Pubmed
Dib-Hajj,
The Na(V)1.7 sodium channel: from molecule to man.
2013,
Pubmed
England,
Subtype-selective targeting of voltage-gated sodium channels.
2009,
Pubmed
Gaskin,
The economic costs of pain in the United States.
2012,
Pubmed
Goldberg,
Loss-of-function mutations in the Nav1.7 gene underlie congenital indifference to pain in multiple human populations.
2007,
Pubmed
King,
Peptide toxins that selectively target insect Na(V) and Ca(V) channels.
2008,
Pubmed
King,
Venoms as a platform for human drugs: translating toxins into therapeutics.
2011,
Pubmed
King,
Spider-venom peptides: structure, pharmacology, and potential for control of insect pests.
2013,
Pubmed
Klinger,
Sea-anemone toxin ATX-II elicits A-fiber-dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons.
2012,
Pubmed
Klint,
Spider-venom peptides that target voltage-gated sodium channels: pharmacological tools and potential therapeutic leads.
2012,
Pubmed
McNamara,
TRPA1 mediates formalin-induced pain.
2007,
Pubmed
Minett,
Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons.
2012,
Pubmed
Mobli,
NMR methods for determining disulfide-bond connectivities.
2010,
Pubmed
Payandeh,
The crystal structure of a voltage-gated sodium channel.
2011,
Pubmed
Reimann,
Pain perception is altered by a nucleotide polymorphism in SCN9A.
2010,
Pubmed
Rong,
Molecular basis of the tarantula toxin jingzhaotoxin-III (β-TRTX-Cj1α) interacting with voltage sensors in sodium channel subtype Nav1.5.
2011,
Pubmed
Rupasinghe,
Localization of Nav 1.7 in the normal and injured rodent olfactory system indicates a critical role in olfaction, pheromone sensing and immune function.
2012,
Pubmed
Saez,
A dynamic pharmacophore drives the interaction between Psalmotoxin-1 and the putative drug target acid-sensing ion channel 1a.
2011,
Pubmed
Santos,
Anti-inflammatory effects and acute toxicity of hydroethanolic extract of Jacaranda decurrens roots in adult male rats.
2012,
Pubmed
Schmalhofer,
ProTx-II, a selective inhibitor of NaV1.7 sodium channels, blocks action potential propagation in nociceptors.
2008,
Pubmed
Szeto,
The MinD membrane targeting sequence is a transplantable lipid-binding helix.
2003,
Pubmed
Undheim,
On the venom system of centipedes (Chilopoda), a neglected group of venomous animals.
2011,
Pubmed
Wei,
Analgesic and anti-inflammatory effects of the amphibian neurotoxin, anntoxin.
2011,
Pubmed
Weiss,
Loss-of-function mutations in sodium channel Nav1.7 cause anosmia.
2011,
Pubmed
Wilson,
μ-Conotoxins that differentially block sodium channels NaV1.1 through 1.8 identify those responsible for action potentials in sciatic nerve.
2011,
Pubmed
,
Xenbase
Xiao,
Jingzhaotoxin-III, a novel spider toxin inhibiting activation of voltage-gated sodium channel in rat cardiac myocytes.
2004,
Pubmed
Yang,
Chemical punch packed in venoms makes centipedes excellent predators.
2012,
Pubmed
Yang,
Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia.
2004,
Pubmed
Yu,
Overview of the voltage-gated sodium channel family.
2003,
Pubmed
