A-134974
A-134974 is a selective adenosine kinase (ADK) inhibitor, with an IC50 of 0.06 nM and 45 nM in rat brain cytoplasmic ADK enzyme assays and intact IMR-32 cells, respectively. A-134974 inhibits adenosine phosphorylation and elevates intracellular and extracellular adenosine levels, alleviates neuropathic tactile allodynia and inflammatory thermal hyperalgesia via endogenous adenosine signaling in the spinal cord, and shows favorable dose separation between its analgesic effects and motor function impairment. A-134974 can be used in research on neuropathic pain, inflammatory pain, RNA silencing and thermoregulation.
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- CAS 番号: 186141-75-3
- 分子式: C11H14IN5O2
- 分子量:375.17
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
IC50 & Target
[4]|
ADK 0.06 nM (IC50, rat brain cytosolic ADK) |
ADK 45 nM (IC50, IMR-32 Cell) |
体外実験
A-134974 (0.01-100 μM; single incubation for assay) inhibits ADK activity in protein extracts from Nicotiana benthamiana stem tissue in a dose-dependent manner, reducing the relative activity to nearly 0% at 100 μM[2].
A-134974 (0.01-100 μM; 5 days) inhibits GFP-targeted RNA silencing in leaf tissues of Nicotiana benthamiana, which correlates with over 90% reduction in ADK activity at the concentration of 100 μM; moreover, this compound exhibits activity across the concentration range of 0.01 to 100 μM within 5 days[2].
A-134974 (10-11 to 10-4 M; 10-20 min, other assays follow standard protocols) potently and selectively inhibits adenosine kinase in rat brain cytosol (IC50 = 0.06 nM) and in intact IMR-32 human neuroblastoma cells (IC50 = 45 nM), with no significant activity against adenosine receptors, adenosine transporters or adenosine deaminase[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
体内実験
A-134974 (0.25-20 μmol/kg; i.p.; single injection) induces dose-dependent hypothermia in male C57Bl/6 mice, with maximal efficacy achieved at a dose of 5 μmol/kg i.p[3].
A-134974 (10 μmol/kg; i.p.; single injection) induces profound, long-lasting hypothermia in male SWR/J wild-type mice, reducing core body temperature by 10.9 °C to a nadir of 27.3 °C[3].
A-134974 (10 μmol/kg; i.p.; single injection) induces significant hypothermia in male SWR/J A1AR−/− mice (reducing core body temperature by 6.9 °C to a nadir of 31.2 °C) and increases plasma adenosine and inosine levels, demonstrating an A1AR-independent hypothermic effect[3].
A-134974 (10 μmol/kg; i.p.; single injection) co-administered with EHNA (10 mg/kg; i.p.; single injection) does not significantly alter the hypothermic effect of A-134974 in male SWR/J wild-type mice[3].
A-134974 (1-30 μmol/kg; i.p.) potently attenuates carrageenan-induced thermal hyperalgesia in rats with an ED50 of 1.0 μmol/kg, and exhibits a 16-fold greater potency for antihyperalgesia compared to locomotor activity reduction, with no significant rotorod impairment at doses up to 30 μmol/kg[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (adult male, 250-300 g)[1]
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Dosage:1 μmol/kg, 3 μmol/kg, 10 μmol/kg, 30 μmol/kg
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Administration:i.p.; single dose
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Result:Did not alter rotorod fall latency across all time points tested at doses up to 30 μmol/kg.
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Animal Model:C57Bl/6 (male, 8 weeks old, 24-26 g)[3]
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Dosage:0.25 μmol/kg; 1 μmol/kg; 5 μmol/kg; 10 μmol/kg; 20 μmol/kg
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Administration:i.p.; single injection
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Result:Induced a dose-dependent hypothermic response, with maximal effects reached at 5 μmol/kg.
Quantified hypothermic effect as area over the curve of core body temperature reduction; saline controls caused core body temperature reductions of less than 1 °C.
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Animal Model:SWR/J wild-type (male, 26-32 g)[3]
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Dosage:10 μmol/kg
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Administration:i.p.; single injection
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Result:Induced profound, long-lasting hypothermia, with a maximum core body temperature reduction of 10.9 °C to a nadir of 27.3 °C, and an area over the curve of 3633 °C·min.
Core body temperature did not return to baseline within the 7-hour observation period, but all mice survived with normal core body temperature the following day.
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Animal Model:SWR/J A1AR−/− (adenosine 1 receptor-deficient, male, 27-36 g)[3]
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Dosage:10 μmol/kg
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Administration:i.p.; single injection
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Result:Induced long-lasting, profound hypothermia, with a maximum core body temperature reduction of 6.9 °C to a nadir of 31.2 °C, and an area over the curve of 2110 °C·min.
This effect was significantly reduced compared to wild-type SWR/J mice (p < 0.05).
Significantly increased plasma adenosine levels from 145 to 663 pmol/mL (p < 0.05) and plasma inosine levels from 193 to 1058 pmol/mL (p < 0.05).
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Animal Model:SWR/J wild-type (male)[3]
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Dosage:10 μmol/kg A-134974; 10 mg/kg EHNA
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Administration:i.p.; single injection; co-administered
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Result:Produced an area over the curve of 3877 °C·min when co-administered with EHNA, which was not significantly different from the area over the curve of 3303 °C·min induced by A-134974 alone.
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Animal Model:Sprague-Dawley (male, 200-300 g, inflammatory pain model induced by intraplantar λ-carrageenan injection)[4]
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Dosage:1 μmol/kg; 3 μmol/kg; 10 μmol/kg; 30 μmol/kg
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Administration:i.p.; single dose
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Result:Blocked carrageenan-induced thermal hyperalgesia with an ED50 of 1.0 μmol/kg.
Reduced exploratory locomotor activity with an ED50 of 16 μmol/kg.
Did not significantly impair rotorod performance at doses up to 30 μmol/kg.
Produced only an approximately 30% decrease in locomotor activity at doses that completely blocked thermal hyperalgesia.
Showed a ratio of ED50 for locomotor activity reduction to antihyperalgesia of 16, and a ratio for rotorod performance impairment to antihyperalgesia greater than 30.
化学情報
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CAS 番号 186141-75-3
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分子量 375.17
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分子式 C11H14IN5O2
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SMILES
O[C@H]1[C@@H](C[C@@H]([C@H]1O)N)N2C3=NC=NC(N)=C3C(I)=C2
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
[1]. Zhu CZ, et al. A-134974: a novel adenosine kinase inhibitor, relieves tactile allodynia via spinal sites of action in peripheral nerve injured rats. Brain research. 2001 Jun 29;905(1-2):104-10. [Content Brief]
[2]. Wang H, et al. Adenosine kinase inhibition and suppression of RNA silencing by geminivirus AL2 and L2 proteins. Journal of virology. 2005 Jun;79(12):7410-8. [Content Brief]
[3]. Eisner C, et al. Profound hypothermia after adenosine kinase inhibition in A1AR-deficient mice suggests a receptor-independent effect of intracellular adenosine. Pflugers Archiv : European journal of physiology. 2017 Feb;469(2):339-347. [Content Brief]
[4]. Jarvis MF, et al. Comparison of the ability of adenosine kinase inhibitors and adenosine receptor agonists to attenuate thermal hyperalgesia and reduce motor performance in rats. Pharmacology, biochemistry, and behavior. 2002 Oct;73(3):573-81. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
A-134974 関連分類
HY-114901 関連分類
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