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^[1][2][3][4]. In Vitro: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]. In Vivo:A-134974 (1-30 μmol/kg; i.p.; single dose) does not impair motor coordination in naïve rats at doses up to 30 μmol/kg (i.p.)^[1].
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].