| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 100mg |
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| Targets |
UK-78282 HCl targets the voltage-gated potassium channels Kv1.3 and Kv1.4. Kv1.3 is predominantly expressed on the plasma membrane of T lymphocytes and plays a critical role in regulating calcium signaling and T-cell activation. By blocking Kv1.3, UK-78282 HCl inhibits the sustained calcium influx required for T-cell activation, proliferation, and cytokine production. The compound binds to overlapping verapamil residues on the inner surface of the channel pore. Its selectivity for Kv1.3 over other potassium channels (IC50 of 200 nM for Kv1.3 and 170 nM for Kv1.4) makes it a valuable tool for dissecting the specific roles of Kv1.3 in immune function and neuronal excitability.
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| ln Vitro |
In vitro, UK-78282 HCl is a potent and specific blocker of Kv1.3 with an IC50 of 200 nM. It also blocks Kv1.4 with an IC50 of 170 nM. The compound effectively inhibits human T lymphocyte activation in vitro. UK-78282 HCl binds to the inner surface of the channel pore, overlapping with verapamil binding residues. Its potency and selectivity for Kv1.3 have been extensively characterized using electrophysiological techniques. The compound's ability to inhibit T-cell activation makes it a valuable tool for studying immune function and for exploring the therapeutic potential of Kv1.3 blockade in autoimmune diseases.
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| ln Vivo |
In vivo, UK-78282 HCl has been studied for its potential applications in autoimmune diseases, transplant rejection, and neurodegenerative diseases. By blocking Kv1.3 and inhibiting T-cell activation, the compound has the potential to modulate immune responses and reduce inflammation. Its ability to cross the blood-brain barrier and modulate neuronal excitability makes it relevant for studying neurodegenerative diseases such as Alzheimer's and Parkinson's. However, detailed in vivo efficacy data are limited, and further studies are needed to fully characterize its therapeutic potential.
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| Enzyme Assay |
In vitro enzyme/receptor binding (non-cell) assays for UK-78282 HCl are typically performed using radioligand binding assays with membrane preparations from cells expressing Kv1.3 or Kv1.4. The membranes are incubated with a radiolabeled potassium channel ligand (e.g., [¹²⁵I]-margatoxin or [³H]-dendrotoxin) and varying concentrations of UK-78282 HCl. Binding affinity (IC50 or Ki) is determined by competitive displacement of the radiolabeled ligand. However, the primary method for characterizing potassium channel blockers is electrophysiology. Patch-clamp electrophysiology in cell-free or whole-cell configurations is used to measure the compound's effects on Kv1.3 and Kv1.4 currents.
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| Cell Assay |
In vitro cell-based experiments for UK-78282 HCl are conducted using primary human T lymphocytes or T-cell lines. Cells are treated with UK-78282 HCl at varying concentrations, and T-cell activation is assessed by measuring proliferation (e.g., [³H]-thymidine incorporation), cytokine production (e.g., IL-2, IFN-γ by ELISA), and expression of activation markers (e.g., CD25, CD69 by flow cytometry). Calcium influx is measured using fluorescent calcium indicators to confirm Kv1.3 blockade. IC50 values for inhibition of T-cell activation are calculated from dose-response curves.
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| Animal Protocol |
In vivo animal experiments for UK-78282 HCl are performed in animal models of autoimmune diseases (e.g., experimental autoimmune encephalomyelitis, rheumatoid arthritis) and transplant rejection. The compound is administered orally or intravenously, and disease severity, immune cell infiltration, and cytokine production are assessed. In models of neurodegenerative diseases, the compound's effects on neuronal excitability, synaptic plasticity, and neuroprotection are evaluated. However, detailed in vivo efficacy data are limited and further studies are needed.
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| ADME/Pharmacokinetics |
UK-78282 HCl is a small molecule (MW 466.05) with physicochemical properties suitable for oral or intravenous administration. The compound's molecular weight (466.05) and lipophilicity support its ability to cross biological membranes and reach target tissues. Detailed pharmacokinetic parameters, including bioavailability, half-life, and clearance, are available from preclinical studies. Its ability to cross the blood-brain barrier makes it relevant for studying CNS disorders.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies have been conducted to evaluate the safety profile of UK-78282 HCl. The compound is well-tolerated at therapeutic doses in animal models, with no significant off-target toxicity reported in available literature. However, as a potassium channel blocker, potential effects on cardiac repolarization (QT prolongation) should be considered. The safety profile of UK-78282 HCl supports its use as a research tool for studying Kv1.3 biology and T-cell function.
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| References | |
| Additional Infomation |
UK-78282 HCl is also known as UK-78282 monohydrochloride. It is a research compound used primarily for studying the role of Kv1.3 in T-cell activation and immune function, as well as for exploring the therapeutic potential of Kv1.3 blockade in autoimmune diseases, transplant rejection, and neurodegenerative diseases. The compound has not been approved for clinical use and remains an investigational agent for research purposes only. Its potent and selective inhibition of Kv1.3 makes it a valuable tool for immunology and neuropharmacology research.
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| Molecular Formula |
C29H36CLNO2
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|---|---|
| Molecular Weight |
466.06
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| Exact Mass |
465.243
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| CAS # |
136647-02-4
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| Related CAS # |
191217-42-2;136647-02-4 (HCl);
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| PubChem CID |
53393337
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| Appearance |
White to off-white solid powder
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| LogP |
6.885
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
10
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| Heavy Atom Count |
33
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| Complexity |
465
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC=C(CCCN2CCC(COC(C3=CC=CC=C3)C4=CC=CC=C4)CC2)C=C1.[H]Cl
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| InChi Key |
ZZSQARULZYQMIG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C29H35NO2.ClH/c1-31-28-16-14-24(15-17-28)9-8-20-30-21-18-25(19-22-30)23-32-29(26-10-4-2-5-11-26)27-12-6-3-7-13-27;/h2-7,10-17,25,29H,8-9,18-23H2,1H3;1H
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| Chemical Name |
4-(benzhydryloxymethyl)-1-[3-(4-methoxyphenyl)propyl]piperidine;hydrochloride
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| Synonyms |
UK78282 Hydrochloride; UK 78282 Hydrochloride; UK-78282 Hydrochloride
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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, 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)
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| Solubility (In Vitro) |
DMSO: ~100 mg/mL (~214.6 mM; with ultrasonication)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.36 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.36 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of 20% SBE-β-CD saline and mix well. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (5.36 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1456 mL | 10.7282 mL | 21.4565 mL | |
| 5 mM | 0.4291 mL | 2.1456 mL | 4.2913 mL | |
| 10 mM | 0.2146 mL | 1.0728 mL | 2.1456 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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