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SL327

CAS No. : 305350-87-2

MCE 站：SL327

产品活性：SL327 抑制 MEK1 和 MEK2，IC₅₀ 分别为 180 nM 和 220 nM。

研究领域：MAPK/ERK Pathway

作用靶点：MEK

In Vitro: The specificity of SL327 for MEK is investigated. Kinase activity is assessed by measuring the incorporation of [32P]phosphate during phosphorylation of substrate peptides specific for each kinase. Although SL327 inhibits MEK with an IC₅₀ of 0.27 μM, 10 μM SL327 has no significant effect on PKA, CaMKII, or PKC.

In Vivo: SL327, which crosses the blood-brain barrier, is administered intraperitoneally at several concentrations to animals prior to cue and contextual fear conditioning. Administration of SL327 completely blocks contextual fear conditioning and significantly attenuates cue learning when measure 24 hr after training. Animals treated with SL327 exhibit significant attenuation of water maze learning; they take significantly longer to find a hidden platform compared with vehicle-treated controls and also fail to use a selective search strategy during subsequent probe trials in which the platform is removed. Mice are injected with various concentrations of SL327 (10, 30, 50 mg/kg i.p.), and 1 hr later their hippocampi are removed and assayed for activated MAPK. SL327 attenuates phosphorylated MAPK levels in a dose-dependent manner. Administration of 10, 30, or 50 mg/kg SL327 significantly attenuates p42 phospho-MAPK levels (F=20.90, P<0.0001;10 mg/kg SL327 vs. vehicle, P<0.05, and 30 and 50 mg/kg SL327 vs. vehicle, P<0.001). Injection with 30 or 50 mg/kg SL327 also significantly reduces p44 phospho-MAPK levels (F=5.627, P<0.005;30 mg/kg vs. vehicle, P<0.05, and 50 mg/kg SL327 vs. vehicle, P<0.01).

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