| Size | Price | Stock | Qty |
|---|---|---|---|
| 500μg |
|
||
| 1mg | |||
| Other Sizes |
| Targets |
Margatoxin is a highly potent and selective inhibitor of the voltage-gated potassium channel Kv1.3 (Kd = 11.7 pM). It also exhibits high affinity for Kv1.2 (Kd = 6.4 pM) and moderate affinity for Kv1.1 (Kd = 4.2 nM). It displays no significant effect on calcium-activated potassium channels, demonstrating selectivity within the Kv channel family. The Kv1.3 channel is a critical regulator of T-lymphocyte activation and is considered a therapeutic target for autoimmune diseases such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis.
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|---|---|
| ln Vitro |
Margatoxin potently blocks Kv1.3 channels (IC50 = 36 pM) in patch-clamp electrophysiology studies using heterologously expressed channels in HEK293 or CHO cells. It reduces VEGF-induced transmembrane calcium influx and nitric oxide production in human endothelial cells. In T-lymphocyte functional assays, Kv1.3 blockade by Margatoxin suppresses calcium signaling and downstream T-cell activation, including proliferation and cytokine production, without affecting cell viability at relevant concentrations.
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| ln Vivo |
In 12-week-old C57BL6/J samples, margaritoxin (ip; 1 pmol/g) dramatically inhibited thioglycolate-induced peritoneal leukocyte migration [2].
In vivo, Margatoxin has been used in rodent models of autoimmune disease to validate Kv1.3 as a therapeutic target. Administration of the toxin has been reported to suppress delayed-type hypersensitivity responses and ameliorate disease severity in experimental autoimmune encephalomyelitis (EAE, a model of multiple sclerosis) and other T-cell-mediated inflammatory conditions. The in vivo efficacy is attributed to the inhibition of Kv1.3 channels on effector memory T-cells (TEM), which are preferentially sensitive to Kv1.3 blockade. |
| Enzyme Assay |
For radioligand binding assays, Margatoxin can be radiolabeled with ¹2⁵I using the chloramine-T method to produce ¹2⁵I-Margatoxin. Membrane preparations from cells expressing Kv1.3 channels (e.g., CHO-Kv1.3 cells) are incubated with ¹2⁵I-Margatoxin (20-50 pM) in binding buffer (50 mM HEPES, pH 7.4, 0.1% BSA) for 2 hours at 4degC. Nonspecific binding is determined in the presence of 100 nM unlabeled Margatoxin. Bound radioactivity is separated by filtration through polyethyleneimine-treated glass fiber filters and counted.
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| Cell Assay |
For electrophysiology studies, HEK293 cells stably expressing Kv1.3 (or other Kv channels) are cultured and whole-cell patch-clamp recordings are performed. Cells are bathed in extracellular solution and held at -80 mV with a step depolarization to +50 mV for 200-500 ms to activate Kv currents. Margatoxin is applied via perfusion at concentrations ranging from 1 pM to 100 nM. Current inhibition is measured, and the half-maximal inhibitory concentration and dissociation constants are derived from concentration-response curves.
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| Animal Protocol |
In a typical in vivo efficacy study for autoimmune disease models, 6-8 week old female C57BL/6 mice are immunized with myelin oligodendrocyte glycoprotein (MOG35-55) peptide emulsified in complete Freund‘s adjuvant to induce experimental autoimmune encephalomyelitis (EAE). Mice are scored daily for clinical signs of paralysis on a scale of 0-5. Margatoxin (0.05-0.2 mg/kg) is administered intraperitoneally or intrathecally starting at disease onset (day 10-14 post-immunization) for 5-10 consecutive days. Clinical scores, body weight, and survival are monitored. CNS infiltration of immune cells is assessed histologically post-treatment.
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| ADME/Pharmacokinetics |
As a peptide toxin administered by injection, Margatoxin is expected to have a relatively short plasma half-life due to proteolytic degradation and rapid renal clearance. Its molecular weight of approximately 4178 Da is below the renal filtration cutoff, leading to rapid elimination. When administered systemically, Margatoxin can access peripheral tissues but has limited ability to cross the blood-brain barrier, making intrathecal injection necessary for studying central nervous system targets. Detailed PK parameters have not been fully published.
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| Toxicity/Toxicokinetics |
Margatoxin is a highly potent peptide toxin with toxicity attributed to its mechanism of Kv channel blockade. At high doses, systemic administration can lead to adverse effects including neuromuscular dysfunction, seizures, respiratory distress, and potentially death due to disruption of normal neuronal and cardiac potassium channel function. In research settings, it is used at sub-toxic, pharmacologically active concentrations (sub-nanomolar to low nanomolar) that achieve selective Kv1.3 blockade without overt toxicity. Formal toxicology studies have not been conducted for this research tool.
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| References | |
| Additional Infomation |
Margatoxin (CAS# 145808-47-5) is a research-grade scorpion toxin widely used in ion channel pharmacology and drug discovery. It is not an approved therapeutic drug. The peptide has a molecular weight of approximately 4178 Da and consists of 39 amino acids with three disulfide bridges. Due to its high potency and selectivity for Kv1.3, Margatoxin serves as a standard pharmacological tool to validate Kv1.3 as a therapeutic target for autoimmune diseases, transplant rejection, and neuroinflammatory disorders. It is also employed in studies investigating memory T-cell biology and calcium signaling.
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| Molecular Formula |
C178H286N52O50S7
|
|---|---|
| Molecular Weight |
4178.94883999997
|
| Exact Mass |
4176.951
|
| CAS # |
145808-47-5
|
| Related CAS # |
Margatoxin TFA
|
| PubChem CID |
121596045
|
| Appearance |
White to off-white solid powder
|
| LogP |
-14.9
|
| Hydrogen Bond Donor Count |
53
|
| Hydrogen Bond Acceptor Count |
65
|
| Rotatable Bond Count |
75
|
| Heavy Atom Count |
287
|
| Complexity |
9830
|
| Defined Atom Stereocenter Count |
40
|
| SMILES |
NCCCCC1NC(=O)CNC(=O)C(CC(=O)N)NC(=O)C(CCSC)NC(=O)C2NC(C(NC(C(NC(CNC(C(NC(C(NC(C(NC(CNC(C(NC(C(NC(C(NC(C(NC(=O)C3NC(C4CCCN4C(C4CCCN4C(C(NC(C(NC(C(NC(C(NC(C4CCCN4C(C(NC(C(NC(C(NC(C(NC(C(NC(C(NC(C(NC(C(C(CC)C)NC(C(C(O)C)N)=O)=O)C(CC)C)=O)CC(=O)N)=O)C(C)C)=O)CCCCN)=O)CSSC2)=O)C(O)C)=O)CO)=O)=O)CCCCN)=O)CCC(=O)N)=O)CSSCC(C(NC(C(NC(C(NC(C(N2CCCC2C(NC(CC2=CN=CN2)C(=O)O)=O)=O)CC2=CC=C(O)C=C2)=O)CSSC3)=O)CCCCN)=O)NC1=O)=O)CC(C)C)=O)=O)=O)CCCCN)=O)C)=O)CCC(=O)N)=O)CC1=CC=CC=C1)=O)=O)CCC(=O)N)=O)CO)=O)C)=O)=O)C)=O)CCCCN)=O
|
| InChi Key |
OVJBOPBBHWOWJI-FYNXUGHNSA-N
|
| InChi Code |
InChI=1S/C178H286N52O50S7/c1-15-91(7)140(225-172(273)141(92(8)16-2)224-169(270)138(190)96(12)233)171(272)211-114(75-134(189)240)158(259)223-139(90(5)6)170(271)208-107(43-25-31-64-184)153(254)221-125-87-287-283-83-121-161(262)206-111(58-69-281-14)157(258)210-113(74-133(188)239)147(248)194-78-136(242)199-102(38-20-26-59-179)149(250)217-120-82-282-284-84-122(220-156(257)110(54-57-132(187)238)205-150(251)106(42-24-30-63-183)207-166(267)126-44-33-66-228(126)176(277)119(81-232)216-173(274)142(97(13)234)226-165(125)266)163(264)212-115(70-89(3)4)174(275)230-68-35-47-129(230)177(278)229-67-34-46-128(229)168(269)222-124(86-286-285-85-123(219-152(253)105(204-160(120)261)41-23-29-62-182)164(265)213-116(72-99-48-50-101(235)51-49-99)175(276)227-65-32-45-127(227)167(268)214-117(178(279)280)73-100-76-191-88-195-100)162(263)203-103(39-21-27-60-180)148(249)198-95(11)145(246)202-109(53-56-131(186)237)155(256)209-112(71-98-36-18-17-19-37-98)146(247)193-79-137(243)200-108(52-55-130(185)236)154(255)215-118(80-231)159(260)197-93(9)143(244)192-77-135(241)196-94(10)144(245)201-104(151(252)218-121)40-22-28-61-181/h17-19,36-37,48-51,76,88-97,102-129,138-142,231-235H,15-16,20-35,38-47,52-75,77-87,179-184,190H2,1-14H3,(H2,185,236)(H2,186,237)(H2,187,238)(H2,188,239)(H2,189,240)(H,191,195)(H,192,244)(H,193,247)(H,194,248)(H,196,241)(H,197,260)(H,198,249)(H,199,242)(H,200,243)(H,201,245)(H,202,246)(H,203,263)(H,204,261)(H,205,251)(H,206,262)(H,207,267)(H,208,271)(H,209,256)(H,210,258)(H,211,272)(H,212,264)(H,213,265)(H,214,268)(H,215,255)(H,216,274)(H,217,250)(H,218,252)(H,219,253)(H,220,257)(H,221,254)(H,222,269)(H,223,259)(H,224,270)(H,225,273)(H,226,266)(H,279,280)/t91-,92-,93-,94-,95-,96+,97+,102-,103-,104-,105-,106-,107-,108-,109-,110-,111-,112-,113-,114-,115-,116-,117-,118-,119-,120-,121-,122-,123-,124-,125-,126-,127-,128-,129-,138-,139-,140-,141-,142-/m0/s1
|
| Chemical Name |
(2S)-2-[[(2S)-1-[(2S)-2-[[(aS,1R,3aS,4S,10S,16S,19R,22S,25S,28S,34S,37S,40R,45R,48S,51S,57S,60S,63S,69S,72S,75S,78S,85R,88S,91R,94S)-40-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-4-amino-2-[[(2S,3S)-2-[[(2S,3S)-2-[[(2S,3R)-2-amino-3-hydroxybutanoyl]amino]-3-methylpentanoyl]amino]-3-methylpentanoyl]amino]-4-oxobutanoyl]amino]-3-methylbutanoyl]amino]hexanoyl]amino]-25,48,78,88,94-pentakis(4-aminobutyl)-a-(2-amino-2-oxoethyl)-22,63,72-tris(3-amino-3-oxopropyl)-69-benzyl-37-[(1R)-1-hydroxyethyl]-34,60-bis(hydroxymethyl)-51,57,75-trimethyl-16-(2-methylpropyl)-3a-(2-methylsulfanylethyl)-2a,3,5a,9,15,18,21,24,27,33,36,39,47,50,53,56,59,62,65,68,71,74,77,80,87,90,93,96,99-nonacosaoxo-7a,8a,42,43,82,83-hexathia-1a,2,4a,8,14,17,20,23,26,32,35,38,46,49,52,55,58,61,64,67,70,73,76,79,86,89,92,95,98-nonacosazahexacyclo[43.35.25.419,91.04,8.010,14.028,32]nonahectane-85-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-imidazol-5-yl)propanoic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| 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
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|---|---|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.2393 mL | 1.1965 mL | 2.3929 mL | |
| 5 mM | 0.0479 mL | 0.2393 mL | 0.4786 mL | |
| 10 mM | 0.0239 mL | 0.1196 mL | 0.2393 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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