XEP-018, also known as μ-conotoxin Cn IIIC, is a biomimetic of natural cone peptides from poisonous marine cone snails (Conus consors). Biologically, it works as a modulator of neuromuscular transmission, as well as a potent and specific blocker of the voltage-gated sodium channel Nav 1.4. Cosmetically, it works as an instant relaxant, giving the skin a smooth appearance.

Physicochemical Properties

Molecular Formula	C92H139N35O28S6
Molecular Weight	2375.7
Exact Mass	2373.89
Elemental Analysis	C, 46.51; H, 5.90; N, 20.64; O, 18.86; S, 8.10
CAS #	936616-33-0
Related CAS #	µ-Conotoxin-CnIIIC acetate
Sequence	{Glp}-Gly-Cys-Cys-Asn-Gly-Pro-Lys-Gly-Cys-Ser-Ser-Lys-Trp-Cys-Arg-Asp-His-Ala-Arg-Cys-Cys-NH2 (Disulfide bridge: Cys3-Cys15, Cys4-Cys21, Cys10-Cys22)
SequenceShortening	{Glp}-GCCNGPKGCSSKWCRDHARCC-NH2 (Disulfide bridge: Cys3-Cys15, Cys4-Cys21, Cys10-Cys22)
Appearance	Typically exists as solid at room temperature
Density	1.71±0.1 g/cm3
SMILES	O=C(N[C@]1([H])C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@]2([H])CSSC[C@](C(N[C@H](C(NCC(N3[C@](CCC3)([H])C(N[C@H](C(NCC(N[C@](CSSC[C@H](NC2=O)C(N)=O)([H])C(N[C@H](C(N[C@H](C(N[C@H](C(N4)=O)CCCCN)=O)CO)=O)CO)=O)=O)=O)CCCCN)=O)=O)=O)CC(N)=O)=O)([H])NC([C@H](CSSC1)NC(CNC([C@@H]5CCC(N5)=O)=O)=O)=O)=O)CCCNC(N)=N)=O)C)=O)CC6=CN=CN6)=O)CC(O)=O)=O)CCCNC(N)=N)=O)[C@@H]4CC7=CNC8=CC=CC=C78
InChi Key	PQKXBHZHSUVYIL-XAASTXGFSA-N
InChi Code	InChI=1S/C92H139N35O28S6/c1-43-73(138)113-50(15-8-22-102-91(97)98)79(144)124-64-41-161-160-40-63-88(153)119-55(27-66(95)130)76(141)107-33-70(134)127-24-10-17-65(127)90(155)116-48(13-4-6-20-93)74(139)105-31-68(132)111-60(37-157-156-36-59(72(96)137)123-89(64)154)85(150)122-58(35-129)84(149)121-57(34-128)83(148)114-49(14-5-7-21-94)77(142)117-53(25-44-29-104-47-12-3-2-11-46(44)47)81(146)125-62(39-159-158-38-61(86(151)126-63)112-69(133)32-106-75(140)52-18-19-67(131)110-52)87(152)115-51(16-9-23-103-92(99)100)78(143)120-56(28-71(135)136)82(147)118-54(80(145)109-43)26-45-30-101-42-108-45/h2-3,11-12,29-30,42-43,48-65,104,128-129H,4-10,13-28,31-41,93-94H2,1H3,(H2,95,130)(H2,96,137)(H,101,108)(H,105,139)(H,106,140)(H,107,141)(H,109,145)(H,110,131)(H,111,132)(H,112,133)(H,113,138)(H,114,148)(H,115,152)(H,116,155)(H,117,142)(H,118,147)(H,119,153)(H,120,143)(H,121,149)(H,122,150)(H,123,154)(H,124,144)(H,125,146)(H,126,151)(H,135,136)(H4,97,98,102)(H4,99,100,103)/t43-,48-,49-,50-,51-,52-,53-,54-,55-,56-,57-,58-,59-,60-,61-,62-,63-,64-,65-/m0/s1
Chemical Name	2-((3S,9R,12S,15S,18S,21S,24R,27S,30S,33S,36S,39S,42R,47R,50S,58aS,61R,68R)-33-((1H-imidazol-5-yl)methyl)-21-((1H-indol-3-yl)methyl)-50-(2-amino-2-oxoethyl)-3,18-bis(4-aminobutyl)-68-carbamoyl-27,39-bis(3-guanidinopropyl)-12,15-bis(hydroxymethyl)-36-methyl-1,4,7,10,13,16,19,22,25,28,31,34,37,40,48,51,54,60,66-nonadecaoxo-61-(2-((S)-5-oxopyrrolidine-2-carboxamido)acetamido)tetrapentacontahydro-1H,46H-47,24-(epiminopropanodithiomethano)-9,42-(methanodithioethanoiminomethano)pyrrolo[2,1-t1][1,2]dithia[5,8,11,14,17,20,23,26,29,32,35,38,41,44,47,50,53]heptadecaazacyclohexapentacontin-30-yl)acetic acid
Synonyms	Mu-Conotoxin; XEP-018; CONOTOXIN; ACETY TETRAPEPTIDE-9; Cono Antiwrinkle; 936616-33-0; μ-Conotoxin Cn IIIC
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Voltage-gated sodium channels (NaV1.4, NaV1.2, NaV1.7, NaV1.5, NaV1.8). NaV1.4 and NaV1.2 are most sensitive, NaV1.7 shows intermediate sensitivity, while NaV1.5 and NaV1.8 are insensitive to µ-conopeptide CnIIIC [1] Selectively inhibits voltage-gated sodium channel subtype NaV1.4 (IC50 = 8.7 nM). Minimal activity against NaV1.1–1.3, 1.5–1.7 (IC50 > 1 μM). [1]
ln Vitro	Channel Blockade Profile: µ-conopeptide CnIIIC potently blocks human and rodent NaV1.4 channels. At -20 mV, application of 1 µM toxin resulted in nearly irreversible blockade of NaV1.4 current, leaving a residual current of ~5%, indicating partial Na⁺ ion passage through occupied channels. TTX (tetrodotoxin) was excluded from the binding site but trapped within the pore by the toxin. For NaV1.2, NaV1.7, NaV1.5, and NaV1.8 channels, 1 µM toxin induced varying degrees of current reduction, with NaV1.5 and NaV1.8 showing minimal response [1]
ln Vivo	utaneous Delivery via Iontophoresis: In porcine ear and human abdominal skin, iontophoretic delivery of µ-conopeptide CnIIIC (XEP-018) significantly increased skin deposition compared to passive diffusion. At current densities of 0.1, 0.3, and 0.5 mA/cm² for 2 hours, skin deposition reached 22.4 ± 0.4, 34.5 ± 1.4, and 57.4 ± 7.6 µg/cm², respectively (vs. passive controls: 9.8 ± 1.1 µg/cm²). Prolonging treatment to 4 hours further increased deposition to 90.9 ± 30.8 µg/cm² at 0.5 mA/cm². Co-iontophoresis with acetaminophen reduced convective solvent flow, decreasing acetaminophen permeation by ~7-fold, confirming XEP-018’s presence in the skin [2]
Enzyme Assay	Patch-Clamp Electrophysiology: HEK293 or Neuro-2a cells transfected with human NaV channel α-subunits were voltage-clamped using the whole-cell configuration. Cells were superfused with extracellular solution containing 1 µM µ-conopeptide CnIIIC, and currents were recorded at various test potentials (-20 mV for NaV1.4/1.2/1.7/1.5; 10 mV for NaV1.8). Toxin-induced current blockade was analyzed for kinetics (onset/offset) and steady-state inhibition. For NaV1.4, irreversible block with residual current was observed, while other subtypes showed variable sensitivity [1]
Cell Assay	Cell Culture and Transfection: HEK293 cells were cultured in DMEM supplemented with 10% FBS and transfected with plasmids encoding human NaV1.4, NaV1.2, NaV1.7, NaV1.5, or NaV1.8 α-subunits plus β-subunits. After 24–48 hours, transfected cells were used for patch-clamp experiments to measure toxin-induced current changes. Neuro-2a cells expressing NaV1.8 were similarly prepared and tested [1]
Animal Protocol	Porcine Skin Model: Full-thickness porcine ear skin was mounted in Franz diffusion cells. XEP-018 solution (0.1–1 mM) was applied to the epidermal side, with iontophoresis delivered via Ag/AgCl electrodes (anodal or cathodal) at 0.1–0.5 mA/cm² for 15–240 minutes. Skin samples were analyzed for peptide deposition via HPLC or fluorescence microscopy (FITC-labeled XEP-018) [2]
ADME/Pharmacokinetics	Skin Absorption: Iontophoretic delivery enhanced XEP-018 penetration into the epidermis, with deposition increasing linearly with current density and treatment duration. Maximum deposition occurred in the stratum corneum and viable epidermis, with minimal systemic absorption detected in vitro [2]
References	[1]. Mechanism and molecular basis for the sodium channel subtype specificity of µ-conopeptide CnIIIC. Br J Pharmacol. 2012 Oct;167(3):576-86. [2]. Cutaneous iontophoresis of μ-conotoxin CnIIIC-A potent NaV1.4 antagonist with analgesic, anaesthetic and myorelaxant properties. Int J Pharm. 2017 Feb 25;518(1-2):59-65. [3]. Natural peptides to drugs - fourth international congress. IDrugs. 2010 Jun;13(6):369-71.
Additional Infomation	Mechanism of Action: µ-conopeptide CnIIIC acts as a pore-blocking antagonist, binding within the NaV channel’s outer vestibule to prevent ion flux. Its specificity for NaV1.4/1.2/1.7 over cardiac NaV1.5 reduces risk of cardiovascular side effects [1] - Clinical Relevance: The toxin’s dual roles in muscle relaxation (via NaV1.4 blockade) and analgesia (via NaV1.7 modulation) make it a candidate for topical treatment of wrinkles and pain. Iontophoretic delivery offers controlled, localized drug release [2]

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	0.4209 mL	2.1046 mL	4.2093 mL
	5 mM	0.0842 mL	0.4209 mL	0.8419 mL
	10 mM	0.0421 mL	0.2105 mL	0.4209 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.