Dalazatide (ShK-186) TFA is a specific peptide inhibitor of Kv1.3 potassium channel. Dalazatide TFA may be utilized in the research of autoimmune diseases such as multiple sclerosis (MS), lupus, psoriasis, rheumatoid arthritis, type 1 diabetes and inflammatory bowel disease.

Physicochemical Properties

Molecular Formula	C186H297F3N57PS7
Molecular Weight	4556.10
Related CAS #	Dalazatide;1081110-69-1
Sequence	H-{pY}-{AEEA}-Arg-Ser-Cys-Ile-Asp-Thr-Ile-Pro-Lys-Ser-Arg-Cys-Thr-Ala-Phe-Gln-Cys-Lys-His-Ser-Met-Lys-Tyr-Arg-Leu-Ser-Phe-Cys-Arg-Lys-Thr-Cys-Gly-Thr-Cys-NH2 (disulfide bridge:Cys5-Cys37,Cys14-Cys30,Cys19-Cys34)
SequenceShortening	H-{pY}-{AEEA}-RSCIDTIPKSRCTAFQCKHSMKYRLSFCRKTCGTC-NH2 (disulfide bridge:Cys5-Cys37,Cys14-Cys30,Cys19-Cys34)
Appearance	White to off-white solid powder
Chemical Name	2-[(1R,2aS,4S,7S,10S,13S,19S,22S,25S,28S,31R,36R,39S,48S,51S,54S,57R,60S,63S,66S,69S,72S,75S,78S,81S,84S,87S,90R,93S,96S,99S)-31-[[(2S)-2-[[(2R)-2-[acetyl-[(2S)-2-amino-3-(4-phosphonooxyphenyl)propanoyl]amino]-2-[2-(2-aminoethoxy)ethoxy]-5-carbamimidamidopentanoyl]amino]-3-hydroxypropanoyl]amino]-10,51,75,87-tetrakis(4-aminobutyl)-93-(3-amino-3-oxopropyl)-60,96-dibenzyl-19,28-bis[(2S)-butan-2-yl]-4,54,69-tris(3-carbamimidamidopropyl)-36-carbamoyl-2a,22,39,48-tetrakis[(1R)-1-hydroxyethyl]-7,63,81-tris(hydroxymethyl)-72-[(4-hydroxyphenyl)methyl]-84-(1H-imidazol-4-ylmethyl)-99-methyl-66-(2-methylpropyl)-78-(2-methylsulfanylethyl)-1a,3,4a,6,9,12,18,21,24,27,30,38,41,44,47,50,53,56,59,62,65,68,71,74,77,80,83,86,89,92,95,98-dotriacontaoxo-6a,7a,10a,11a,33,34-hexathia-a,2,3a,5,8,11,17,20,23,26,29,37,40,43,46,49,52,55,58,61,64,67,70,73,76,79,82,85,88,91,94,97-dotriacontazatetracyclo[55.47.4.445,90.013,17]dodecahectan-25-yl]acetic acid TFA salt
Synonyms	Dalazatide TFA salt; Dalazatide [INN]; SHK-186; UNII-6U0259J807; 1081110-69-1; 6U0259J807; o-PHOSPHONO-L-Tyrosyl-2-(2-(2-aminoethoxy)ethoxy)acetyl(potassium channel toxin kappa-stichotoxin-shela stoichactis helianthus (caribbean sea anemone)) peptidamide;
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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
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	Kv1.3[1]; Kv1.3 potassium channel (IC₅₀ = 69 pM for human Kv1.3; >1,000-fold selectivity over related channels including Kv1.1, Kv1.4, Kv1.6, Kv1.7, KCa3.1, and hERG) [1] KV1.3 potassium channel (IC50 = 11 pM) [1][2][3]
ln Vitro	Shakhatide (Dalazatide) (0-1000 pM) With a Kd of 65 ± 5 pM, TFA dose-dependently inhibits Kv1.3 currents in ovary-specific GFP+ effector memory T(Tem) cells [3]. Dalazatide (0–100 nM; 3 days) TFA reduces the proliferation of CCR7− T cells in a way that is dependent on dosage [3]. Dalazatide (100 nM; 30 min) TFA inhibits the calcium signaling pathway, which stops β1 integrin activation and immobilizes effector memory T (Tem) cells at the inflammatory site [3]. Dalazatide selectively inhibits KV1.3 channels on effector memory T cells (TEM), reducing calcium influx and cytokine production (IL-2, IFN-γ) by 70-80% at 100 pM [3]. In human T cells from psoriasis patients, it suppresses proliferation (EC50 = 50 pM) and Th17/Th1 responses [1].
ln Vivo	In vivo, Dalazatide (ShK-186) (100 μg/kg; sc; once) TFA reduces Tem cell motility and activation and prevents delayed-type hypersensitivity in rats [3]. In plaque psoriasis patients (Phase 1b), subcutaneous Dalazatide (2-4 μg/kg twice weekly) improved PASI scores by 40% over 8 weeks with reduced epidermal thickness [1]. In SLE models, it decreased autoantibody production and renal inflammation by targeting pathogenic TEM cells [2].
Cell Assay	Cell Proliferation Assay[3] Cell Types: CCR7− T cell[3] Tested Concentrations: 0-100 nM Incubation Duration: 3 days Experimental Results: Inhibited cell proliferation with an IC50 of 180 ± 37 pM. cell proliferation assay [3] Cell Types: CCR7− T cells [3] Tested Concentrations: 0- 100nM Incubation Duration: 3 days Experimental Results: Inhibits cell proliferation, IC50 is 180±37pM. TEM cells were isolated from human PBMCs or SLE patient blood. Kv1.3 currents were recorded via patch-clamp electrophysiology. Calcium flux was measured using Fluo-4 AM dye after TCR stimulation with anti-CD3/anti-CD28 antibodies [2] Cytokine secretion (IFN-γ, TNF-α, IL-17) was quantified by ELISA following 48-hour TEM cell activation. Proliferation was assessed via [³H]-thymidine incorporation [2] For DTH imaging, murine TEM cells were labeled with CFSE and adoptively transferred. Two-photon intravital microscopy tracked cell motility in ear pinnae after antigen challenge [3]
Animal Protocol	Animal/Disease Models: Lewis rats rats, delayed-type hypersensitivity (DTH) model[3] Doses: 100 μg/kg Route of Administration: subcutaneous (sc) injection, once Experimental Results: decreased DTH at all time points compared to rats given saline injections. Suppressed the proliferation of the Temp cells. Psoriasis trial: Patients received 2-4 μg/kg subcutaneously twice weekly for 8 weeks with dermatologic assessments [1]. Murine DTH model: 1 mg/kg intraperitoneal injection suppressed TEM-mediated inflammation [3].
References	[1]. Dalazatide (ShK-186), a first-in-class peptide inhibitor of Kv1. 3 potassium channels, demonstrates safety, tolerability and proof of concept of efficacy in patients with active plaque psoriasis. J. Invest. Dermatol., 2016, 136(8). [2]. Thu0285 Dalazatide, an Inhibitor of the KV1. 3 Channel on Activated Effector Memory T Cells, Has Immunotherapy Potential in Systemic Lupus Erythematosus. 2016. [3]. Imaging of effector memory T cells during a delayed-type hypersensitivity reaction and suppression by Kv1.3 channel block. Immunity. 2008 Oct 17;29(4):602-14.
Additional Infomation	Dalazatide is a 37-amino acid peptide derived from sea anemone ShK. It treats autoimmune diseases by selectively inhibiting Kv1.3 on TEM cells, which drive chronic inflammation [1][2] Clinical proof-of-concept established for plaque psoriasis; potential applications include SLE, rheumatoid arthritis, and multiple sclerosis [1][2] Mechanism involves suppression of TEM cell activation without broad immunosuppression [3] Dalazatide is a 37-amino acid peptide derived from sea anemone ShK. It treats autoimmune diseases by selectively inhibiting Kv1.3 on TEM cells, which drive chronic inflammation [1][2] Clinical proof-of-concept established for plaque psoriasis; potential applications include SLE, rheumatoid arthritis, and multiple sclerosis [1][2] Mechanism involves suppression of TEM cell activation without broad immunosuppression [3]

Solubility Data

Solubility (In Vitro)

H2O :~100 mg/mL (~21.95 mM)

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	0.2195 mL	1.0974 mL	2.1949 mL
	5 mM	0.0439 mL	0.2195 mL	0.4390 mL
	10 mM	0.0219 mL	0.1097 mL	0.2195 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.