UK-78282
UK-78282 is a KV1.3 channel inhibitor with an IC50 value of 0.20 μM and a Kd of 0.39 μM. UK-78282 also inhibits the Kv1.4 Potassium Channel. UK-78282 blocks KV1.3 in a use-dependent manner and inhibits human T lymphocyte activation by regulating the cell cycle. UK-78282 can be used in research related to mental disorders, such as depression and schizophrenia.
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- CAS. Nr.: 191217-42-2
- Formel: C29H35NO2
- Molecular Weight:429.59
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Speicherung:
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
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Biologische Aktivität
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Chemical Information
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Lösungsmittel & Löslichkeit
- Protokoll
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
Kv1.3 0.2 μM (IC50) |
Kv1.4 |
IL-2 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
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| L929 | IC50 |
200 nM
Compound: UK-78282
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Inhibition of Kv1.3 expressed in mouse L929 cells exposed to depolarizing step pulses from -80 mV to +40 mV by whole cell patch clamp method
Inhibition of Kv1.3 expressed in mouse L929 cells exposed to depolarizing step pulses from -80 mV to +40 mV by whole cell patch clamp method
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[PMID: 23084278] |
| T-cell | IC50 |
0.2 μM
Compound: UK-78282
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In vitro inhibition of human T-cells voltage-gated potassium channel subunit Kv1.3
In vitro inhibition of human T-cells voltage-gated potassium channel subunit Kv1.3
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10.1016/S0960-894X(97)00163-7 |
| T-cell line | IC50 |
0.4 μM
Compound: 14a
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In vitro inhibitory potency against human T-cells Rb efflux
In vitro inhibitory potency against human T-cells Rb efflux
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10.1016/S0960-894X(97)00163-7 |
In Vitro
UK‑78282 blocks Kv1.3 channel function in various cell models. Under acute administration conditions, this compound blocks native Kv1.3 channels in human peripheral blood T lymphoblasts (IC50 = 202 nM), recombinant Kv1.3 channels in L929 cells (IC50 = 280 nM), and Kv1.3 channels in RBL cells (IC50 = 333 nM); it inhibits Kv1.3-mediated 86Rb efflux in human T cells (IC50 = 0.4 μM); and it inhibits the binding of 125I‑ChTX to Kv1.3 expressed in HeLa cells (IC50 = 0.7 μM)[1].
UK‑78282 produces use-dependent block of Kv1.3 channels in human peripheral blood T lymphoblasts; the longer the duration of depolarizing pulses, the faster the establishment of steady-state block. Maintaining the holding potential at -50 mV to increase the proportion of C-type inactivated channels enhances the blocking efficacy of this compound[1].
UK-78282 binds to an internal site of the Kv1.3 channel in human peripheral blood T lymphoblasts. This site overlaps with the binding site of verapamil, but does not overlap with the binding sites of extracellular ChTX or intracellular TEA[1].
UK-78282 exhibits selectivity for Kv1.3 and Kv1.4 channels over other Kv family channels, with negligible activity on T cell KCa channels at concentrations up to 30 μM[1].
UK‑78282 (100 nM; ≥2 min) selectively inhibits action potential firing only in striatal projection neurons of the nucleus accumbens shell in low-motivation (lowS) rats, and slows the inactivation of their A-type potassium currents; this compound reduces the amplitude of A-type potassium currents in such neurons across three groups of rats, namely low-motivation (lowS), high-motivation (highS), and moderate-motivation (midS) rats[1].
UK‑78282 inhibits PHA-induced proliferation of purified human peripheral blood T cells (IC50 = 2.0 μM) by acting on the late G1/early S phase of the cell cycle; it also suppresses PHA-stimulated IL‑2 production (IC50 = 2.9 μM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (male, 250-300 g, low/intermediate/high-motivation model via progressive ratio sucrose self-administration)[2]
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Dosage:1 nM; 100 nM
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Administration:i.c.v. bilateral microinfusion; 0.5 μl/side over 2 min + 1 min diffusion
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Result:Showed no significant effect on PR performance in any motivation group at 1 nM.
Significantly increased PR breakpoints, active lever presses, and sucrose pellets earned in low-motivation rats at 100 nM.
Showed no effect on PR breakpoints, active lever presses, or sucrose pellets earned in intermediate- or high-motivation rats at 100 nM.
Significantly reduced inactive lever presses in high-motivation rats at 100 nM, though this effect was driven by a single outlier and did not alter other high-motivation outcomes.
Chemical Information
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CAS. Nr. 191217-42-2
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Appearance Liquid (Density: 1.061±0.06 g/cm3)
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Molecular Weight 429.59
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Formel C29H35NO2
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Color Pink to red
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SMILES
COC1=CC=C(CCCN2CCC(COC(C3=CC=CC=C3)C4=CC=CC=C4)CC2)C=C1
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
4°C, protect from light
* In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)
Lösungsmittel & Löslichkeit
In Vitro:
DMSO : 25 mg/mL (58.20 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
Protokoll
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Flow cytometric DNA-content cell-cycle staining
Flow cytometric DNA-content cell-cycle staining measures the fluorescence intensity of DNA-bound fluorochromes in single cells or nuclei to estimate DNA content distributions, allowing assignment of populations to G0/G1, S, and G2/M phases by DNA histogram deconvolution. Propidium iodide (PI) intercalates into DNA, and PI fluorescence is proportional to cellular DNA content when staining is performed under conditions that make DNA accessible and minimize non-DNA signal. Cells with G2/M DNA content are expected to show approximately twice the fluorescence intensity of G0/G1 cells, while S-phase cells occupy intermediate fluorescence values. PI-based DNA-content analysis can also detect cells with fractional DNA content, often reported as sub-G1, when DNA fragmentation and extraction during staining reduce retained DNA signal in apoptotic cells. DAPI is an alternative DNA fluorochrome for univariate DNA-content analysis, while bivariate approaches combining DNA content with proliferation
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BrdU Incorporation Assay
Bromodeoxyuridine (BrdU) incorporation assay is based on the principle that BrdU, a thymidine analog, is incorporated into newly synthesized DNA during the S phase of the cell cycle, thereby serving as a marker of DNA replication and cellular proliferation. Incorporated BrdU can be detected using anti-BrdU antibodies following DNA denaturation, enabling visualization or quantification of proliferating cells through immunochemical detection methods such as immunofluorescence or immunohistochemistry.
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Protocol for Cell Cycle
Cell-cycle analysis by flow cytometry measures DNA content in single cells to estimate the fraction of cells in G0/G1, S, and G2/M phases. Propidium iodide intercalates into DNA, and after RNA removal with RNase, fluorescence intensity reflects cellular DNA content: 2N cells are assigned to G0/G1, cells between 2N and 4N to S phase, and 4N cells to G2/M. DNA-content analysis alone cannot reliably separate G0 from G1 or G2 from M. Ki-67 can distinguish quiescent G0 cells from cycling cells, EdU or BrdU incorporation marks active DNA synthesis in S phase, and phospho-histone H3 staining identifies mitotic cells within the 4N population.
Reinheit & Dokumentation
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Data Sheet (280 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
Verweise
[1]. Hanson DC, et al. UK-78,282, a novel piperidine compound that potently blocks the Kv1.3 voltage-gated potassium channel and inhibits human T cell activation. British journal of pharmacology. 1999 Apr;126(8):1707-16. [Content Brief]
[2]. O'Donovan B, et al. Altered gating of K1.4 in the nucleus accumbens suppresses motivation for reward. eLife. 2019 Sep 05;8:e47870. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.3278 mL | 11.6390 mL | 23.2780 mL | 58.1950 mL |
| 5 mM | 0.4656 mL | 2.3278 mL | 4.6556 mL | 11.6390 mL | |
| 10 mM | 0.2328 mL | 1.1639 mL | 2.3278 mL | 5.8195 mL | |
| 15 mM | 0.1552 mL | 0.7759 mL | 1.5519 mL | 3.8797 mL | |
| 20 mM | 0.1164 mL | 0.5820 mL | 1.1639 mL | 2.9098 mL | |
| 25 mM | 0.0931 mL | 0.4656 mL | 0.9311 mL | 2.3278 mL | |
| 30 mM | 0.0776 mL | 0.3880 mL | 0.7759 mL | 1.9398 mL | |
| 40 mM | 0.0582 mL | 0.2910 mL | 0.5820 mL | 1.4549 mL | |
| 50 mM | 0.0466 mL | 0.2328 mL | 0.4656 mL | 1.1639 mL |
UK-78282 Related Classifications
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