CnIIIC (P03834) Protein Card

General Information
Alternative name(s) XEP
Organism Conus consors
Organism region Indo-Pacific
Organism diet piscivorous
Protein Type Wild type
Protein precursor CnIIIC precursor (6155)

CnIIIC has anaesthetic and myorelaxant properties, and has been developped as a cosmetic product (claims to relax wrinkles) and a modified version called XEP(TM)-018 is sold by Activen.

Del Río-Sancho et al. (2017) investigated cutaneous iontophoretic delivery of CnIIIC using porcine ear skin and it was validated using human abdominal skin. Initial results showed that:

  • Cutaneous deposition of XEP following iontophoresis was superior to passive delivery and increased with current density
  • CnIIIC was mainly adsorbed on the skin surface when administered passively
  • CnIIIC was present in the skin as it significantly reduced convective solvent flow as evidenced by the ˜ 7-fold decrease in acetaminophen permeation
  • Skin deposition of XEP was already quantifiable after iontophoresis for 15 min at the lower concentration

  • Classification
    Conopeptide class conotoxin
    Gene superfamily M superfamily
    Cysteine framework III
    Pharmacological family mu conotoxin

    Modified residues
    1ZPyroglutamic acid
    23nh2C-term amidation
    Sequence evidence protein level
    Average Mass NA
    Monoisotopic Mass NA
    Isoelectric Point 11.80
    Extinction Coefficient [280nm] 5500.00


    IC50: Voltage-Gated Sodium Channels

    Nav1.4H. sapiens4.95nM+/-0.5Markgraf,R. et al. (2012)
    R. norvegicus1.3nM+/-0.4Favreau P et al. (2012)

    Percentage inhibition: Voltage-Gated Sodium Channels

    TargetOrganism% inhibitionConcentrationRef
    Nav1.2H. sapiens85+/-51uMMarkgraf,R. et al. (2012)
    Nav1.4H. sapiens95saturationMarkgraf,R. et al. (2012)
    84+/-310uMMarkgraf,R. et al. (2012)
    60+/-101uMMarkgraf,R. et al. (2012)
    R. norvegicus95saturationMarkgraf,R. et al. (2012)
    Nav1.5H. sapiens131uMMarkgraf,R. et al. (2012)
    610uMMarkgraf,R. et al. (2012)
    Nav1.7H. sapiens64+/-51uMMarkgraf,R. et al. (2012)
    82+/-310uMMarkgraf,R. et al. (2012)
    Nav1.8H. sapiens5+/-51uMMarkgraf,R. et al. (2012)
    010uMMarkgraf,R. et al. (2012)

    Biass,D., Dutertre,S., Gerbault,A., Menou,J.L., Offord,R., Favreau,P. and Stöcklin,R. (2009) Comparative proteomic study of the venom of the piscivorous cone snail Conus consors. J Proteomics 72:210-218
    Benoit,E., Favreau,P., Schlumberger,S., Cordova,M.A., Tytgat,J., Stocklin, R. abd and R. Stocklin and Molgo J. (2008) A new mu-conotoxin from Conus consors that atypically targets sodium channels in unmyelinated and myelinated nerve fibers Abstract Book, 16th European Section Meeting of the International Society on Toxinology
    Favreau P, Benoit E, Hocking HG, Carlier L, D hoedt D, Leipold E, Markgraf R, Schlumberger S, Córdova MA, Gaertner H, Paolini-Bertrand M, Hartley O, Tytgat J, Heinemann SH, Bertrand D, Boelens R, Stöcklin R, Molgó J (2012) A novel μ-conopeptide, CnIIIC, exerts potent and preferential inhibition of NaV1.2/1.4 channels and blocks neuronal nicotinic acetylcholine receptors Br J Pharmacol 166:1654-1668
    Violette,A., Biass,D., Dutertre,S., Koua,D., Piquemal,D., Pierrat,F. and Favreau,P. (2012) Large-scale discovery of conopeptides and conoproteins in the injectable venom of a fish-hunting cone snail using a combined proteomic and transcriptomic approach. J Proteomics 75:5215-5225
    Markgraf,R., Leipold,E., Schirmeyer,J., Paolini-Bertrand,M., Hartley,O. and Heinemann,S.H. (2012) Mechanism and molecular basis for the sodium channel subtype specificity of μ-conopeptide CnIIIC. Br. J. Pharmacol. 167:576-586
    Del Río-Sancho,S., Cros,C., Coutaz,B., Cuendet,M. and Kalia,Y.N. (2017) Cutaneous iontophoresis of μ-conotoxin CnIIIC-A potent NaV1.4 antagonist with analgesic, anaesthetic and myorelaxant properties. Int J Pharm 518:59-65

    Internal links
    Protein Precursor CnIIIC precursor (6155)
    Nucleic acids
    Structure Solution structure of the skeletal muscle and neuronal voltage gated sodium channel antagonist mu-conotoxin CnIIIC

    External links
    UniProtKB/Swiss-Prot I1SB07
    Ncbi 2YEN_A, I1SB07