Discovery of a selective NaV1.7 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

Volumn 110, Issue 43, 2013, Pages 17534-17539

  Yang, Shilong ^a,b   Xiao, Yao ^a,b   Kang, Di ^a,b   Liu, Jie ^a,b   Li, Yuan ^a,b   Undheim, Eivind A B ^c   Klint, Julie K ^c   Rong, Mingqiang ^a   Lai, Ren ^a   King, Glenn F ^c  

^a KUNMING INSTITUTE OF ZOOLOGY   (China)

^b UNIVERSITY OF CHINESE ACADEMY OF SCIENCES   (China)

^c UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

Chronic pain; Drug discovery; Peptide therapeutic

Indexed keywords

ACETIC ACID; ANALGESIC AGENT; ARTHROPOD VENOM; MORPHINE; MU SLPTX SSM6A PROTEIN; SODIUM CHANNEL NAV1.7; UNCLASSIFIED DRUG; VOLTAGE GATED SODIUM CHANNEL BLOCKING AGENT; PEPTIDE; SCN9A PROTEIN, HUMAN;

ANALGESIC ACTIVITY; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DISULFIDE BOND; DRUG EFFICACY; DRUG POTENCY; DRUG SELECTIVITY; HEAT; HUMAN; HUMAN CELL; IC 50; MOUSE; NOCICEPTION; NONHUMAN; PAIN; PATCH CLAMP; PRIORITY JOURNAL; RAT; SCOLOPENDRA; SEQUENCE HOMOLOGY; SPINAL GANGLION; AMINO ACID SEQUENCE; ANIMAL; ARTHROPOD; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; FEMALE; GENETICS; HEK293 CELL LINE; MALE; MEMBRANE POTENTIAL; METABOLISM; MOLECULAR GENETICS; NERVE CELL; NUCLEOTIDE SEQUENCE; OOCYTE; PATCH CLAMP TECHNIQUE; PATHOPHYSIOLOGY; PHYSIOLOGY; XENOPUS LAEVIS; CELL STRAIN HEK293; CHRONIC PAIN; DRUG DEVELOPMENT; DRUG EFFECT; PEPTIDE THERAPEUTIC;

AMINO ACID SEQUENCE; ANALGESICS; ANIMALS; ARTHROPOD VENOMS; ARTHROPODS; BASE SEQUENCE; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HEK293 CELLS; HUMANS; MALE; MEMBRANE POTENTIALS; MICE; MOLECULAR SEQUENCE DATA; MORPHINE; NAV1.7 VOLTAGE-GATED SODIUM CHANNEL; NEURONS; OOCYTES; PAIN; PATCH-CLAMP TECHNIQUES; PEPTIDES; RATS; XENOPUS LAEVIS;

CHRONIC PAIN; DRUG DISCOVERY; PEPTIDE THERAPEUTIC;

EID: 84886426830     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1306285110     Document Type: Article

References (40)

1. Brennan F, Carr DB, CousinsM (2007) Pain management: A fundamental human right. Anesth Analg 105(1):205-221.
2. Gaskin DJ, Richard P (2012) The economic costs of pain in the United States. J Pain 13(8):715-724.
3. Payandeh J, Scheuer T, Zheng N, Catterall WA (2011) The crystal structure of a voltage-gated sodium channel. Nature 475(7356):353-358.
4. Basbaum AI, Bautista DM, Scherrer G, Julius D (2009) Cellular and molecular mechanisms of pain. Cell 139(2):267-284.
5. Yu FH, Catterall WA (2003) Overview of the voltage-gated sodium channel family. Genome Biol 4(3):207.
6. V) channels. Channels (Austin) 2(2):100-116.
7. (V)1.7 sodium channel: From molecule to man. Nat Rev Neurosci 14(1):49-62.
8. Cox JJ, et al. (2006) An SCN9A channelopathy causes congenital inability to experience pain. Nature 444(7121):894-898.
9. Minett MS, et al. (2012) Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons. Nat Commun 3:791.
10. Reimann F, et al. (2010) Pain perception is altered by a nucleotide polymorphism in SCN9A. Proc Natl Acad Sci USA 107(11):5148-5153.
11. Weiss J, et al. (2011) Loss-of-function mutations in sodium channel Nav1.7 cause anosmia. Nature 472(7342):186-190.
12. v 1.7 in the normal and injured rodent olfactory system indicates a critical role in olfaction, pheromone sensing and immune function. Channels (Austin) 6(2):103-110.
13. Undheim EA, King GF (2011) On the venom system of centipedes (Chilopoda), a neglected group of venomous animals. Toxicon 57(4):512-524.
14. Yang S, et al. (2012) Chemical punch packed in venoms makes centipedes excellent predators. Mol Cell Proteomics 11(9):640-650.
15. Mobli M, King GF (2010) NMR methods for determining disulfide-bond connectivities. Toxicon 56(6):849-854.
16. Black JA, Frézel N, Dib-Hajj SD, Waxman SG (2012) Expression of Nav1.7 in DRG neurons extends from peripheral terminals in the skin to central preterminal branches and terminals in the dorsal horn. Mol Pain 8:82.
17. Chen J, et al. (2009) Expression and characterization of jingzhaotoxin-34, a novel neurotoxin from the venom of the tarantula Chilobrachys jingzhao. Peptides 30(6): 1042-1048.
18. Bosmans F, et al. (2006) Four novel tarantula toxins as selective modulators of voltage-gated sodium channel subtypes. Mol Pharmacol 69(2):419-429.
19. Bosmans F, Martin-Eauclaire MF, Swartz KJ (2008) Deconstructing voltage sensor function and pharmacology in sodium channels. Nature 456(7219):202-208.
20. McNamara CR, et al. (2007) TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci USA 104(33):13525-13530.
21. King GF (2011) Venoms as a platform for human drugs: Translating toxins into therapeutics. Expert Opin Biol Ther 11(11):1469-1484.
22. Ahmad S, et al. (2007) A stop codon mutation in SCN9A causes lack of pain sensation. Hum Mol Genet 16(17):2114-2121.
23. v1.7 gene underlie congenital indifference to pain in multiple human populations. Clin Genet 71(4): 311-319.
24. Yang Y, et al. (2004) Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. J Med Genet 41(3):171-174.
25. England S, de Groot MJ (2009) Subtype-selective targeting of voltage-gated sodium channels. Br J Pharmacol 158(6):1413-1425.
26. (v)1.6 is localized at nodes of ranvier, dendrites, and synapses. Proc Natl Acad Sci USA 97(10):5616-5620.
27. Klint JK, et al. (2012) Spider-venom peptides that target voltage-gated sodium channels: Pharmacological tools and potential therapeutic leads. Toxicon 60(4): 478-491.
28. V1.7 sodium channels, blocks action potential propagation in nociceptors. Mol Pharmacol 74(5): 1476-1484.
29. Clare JJ (2010) Targeting voltage-gated sodium channels for pain therapy. Expert Opin Investig Drugs 19(1):45-62.
30. King GF, Hardy MC (2013) Spider-venom peptides: Structure, pharmacology, and potential for control of insect pests. Annu Rev Entomol 58:475-496.
31. Xiao Y, et al. (2004) Jingzhaotoxin-III, a novel spider toxin inhibiting activation of voltage-gated sodium channel in rat cardiac myocytes. J Biol Chem 279(25):26220-26226.
32. Beacham D, Ahn M, Catterall WA, Scheuer T (2007) Sites and molecular mechanisms of modulation of Na(v)1.2 channels by Fyn tyrosine kinase. J Neurosci 27(43):11543-11551.
33. Rong M, et al. (2011) Molecular basis of the tarantula toxin jingzhaotoxin-III (β-TRTXCj1α) interacting with voltage sensors in sodium channel subtype Nav1.5. FASEB J 25(9):3177-3185.
34. Wei L, et al. (2011) Analgesic and anti-inflammatory effects of the amphibian neurotoxin, anntoxin. Biochimie 93(6):995-1000.
35. Santos JA, et al. (2012) Anti-inflammatory effects and acute toxicity of hydroethanolic extract of Jacaranda decurrens roots in adult male rats. J Ethnopharmacol 144(3): 802-805.
36. Saez NJ, et al. (2011) A dynamic pharmacophore drives the interaction between Psalmotoxin-1 and the putative drug target acid-sensing ion channel 1a. Mol Pharmacol 80(5):796-808.
37. Szeto TH, Rowland SL, Habrukowich CL, King GF (2003) The MinD membrane targeting sequence is a transplantable lipid-binding helix. J Biol Chem 278(41):40050-40056.
38. Bains NPS, Wilce JA, Mackay LG, King GF (1999) Controlling leucine zipper specificity with interfacial hydrophobic residues. Lett Pept Sci 6:381-390.
39. Klinger AB, et al. (2012) Sea-anemone toxin ATX-II elicits A-fiber-dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons. Mol Pain 8:69.
40. V1.1 through 1.8 identify those responsible for action potentials in sciatic nerve. Proc Natl Acad Sci USA 108(25):10302-10307.