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5mg | ||
10mg | ||
25mg | ||
50mg |
Dalazatide (SHK-186) is a peptide-based blocker of KV1.3 channel used for treating autoimmune diseases. It is a first-in-class and investigational drug that may be used for the treatment of autoimmune diseases such as lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, and multiple sclerosis (MS).
ln Vitro |
In Ova-specific GFP+ effector memory T (Tem) cells, dalacazide (ShK-186) (0-1000 pM) dose-dependently inhibits the Kv1.3 current with a Kd of 65 ± 5 pM[3]. The proliferation of CCR7-positive T cells is inhibited by dalazatide (0-100 nM; 3 days) in a dose-dependent manner[3]. By reducing calcium transmission and blocking β1 integrin activation, dalazatide (100 nM; 30 min) immobilizes effector memory T (Tem) cells at inflammatory sites[3].
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Cell Assay |
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. |
Animal Protocol |
Animal/Disease Models: Lewis rat, delayed-type dalazatide (ShK-186) (100 μg/kg; sc; Once) delays delayed-type hypersensitivity reactions in the dye and dyes the internal movement and activation of Tem cells [3] . Hypersensitivity (DTH) model [3]
Doses: 100 μg/kg Route of Administration: One subcutaneous injection Experimental Results: Compared with rats injected with normal saline, DTH was diminished at all time points. Inhibits the proliferation of Tem cells. |
References |
[1]. Olsen C, et al. 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]. Stevens A M, et al. Thu0285 Dalazatide, an Inhibitor of the KV1. 3 Channel on Activated Effector Memory T Cells, Has Immunotherapy Potential in Systemic Lupus Erythematosus. 2016. [3]. Matheu MP, et al. 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. |
Molecular Formula |
C184H296N57O55PS7
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Molecular Weight |
4442.09673118591
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CAS # |
1081110-69-1
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Related CAS # |
Dalazatide TFA
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Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
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SMILES |
S1C[C@H]2C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@@H]3C(N[C@H](C(N[C@H](C(N[C@@H](CO)C(N[C@@H](CCSC)C(N[C@H](C(N[C@@H](CC4C=CC(=CC=4)O)C(N[C@@H](CCCNC(=N)N)C(N[C@@H](CC(C)C)C(N[C@@H](CO)C(N[C@@H](CC4C=CC=CC=4)C(N[C@H](C(N[C@H](C(N[C@H](C(N[C@H](C(NC(CSSC3)C(NCC(N[C@@H]([C@@H](C)O)C(N[C@H](C(N)=O)CSSC[C@@H](C(N[C@@H]([C@@H](C)CC)C(N[C@@H](CC(=O)O)C(N[C@@H]([C@@H](C)O)C(N[C@@H]([C@@H](C)CC)C(N3CCC[C@H]3C(N[C@H](C(N[C@H](C(N[C@H](C(N2)=O)CCCNC(=N)N)=O)CO)=O)CCCCN)=O)=O)=O)=O)=O)=O)NC([C@H](CO)NC([C@](CCCNC(=N)N)(N(C(C)=O)C([C@H](CC2C=CC(=CC=2)OP(=O)(O)O)N)=O)OCCOCCN)=O)=O)=O)=O)=O)=O)[C@@H](C)O)=O)CCCCN)=O)CCCNC(=N)N)=O)CS1)=O)=O)=O)=O)=O)=O)CCCCN)=O)=O)=O)CC1=CNC=N1)=O)CCCCN)=O)=O)CCC(N)=O)=O)CC1C=CC=CC=1)=O)C)=O)[C@@H](C)O)=O
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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 |
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 | 0.2251 mL | 1.1256 mL | 2.2512 mL | |
5 mM | 0.0450 mL | 0.2251 mL | 0.4502 mL | |
10 mM | 0.0225 mL | 0.1126 mL | 0.2251 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.