SL327 is a selective inhibitor for MEK1/2 with IC50 of 0.18 μM/0.22 μM; able to transport through the blood-brain barrier.

MEK1:0.18 μM, MEK2:0.22 μM

30 mg/Kg SL327明显损害小鼠空间学习记忆.50 mg/kg SL327可以透过血-脑屏障,通过抑制MAPK/ERK磷酸化而抑制条件性恐惧.

SL327对多种其他包括PKA,PKC或CamKII的激酶没有抑制效果。

The ligand binding competition assays are performed. Cytosolic cell extracts from Hepa-1 cells are generated by the resuspension of the cell pellets in HEDG buffer [25 mM Hepes, 1 mM EDTA, 1 mM dithiothreitol, and 10% (v/v) glycerol, pH 7.5] containing 0.4 mM leupeptin, 4 mg/mL aprotinin, and 0.3 mM phenylmethylsulfonyl fluoride, homogenization, and centrifugation at 100,000 g for 45 min. Aliquots of the supernatant (120 μg) are incubated at room temperature for 2 h with the indicated concentrations of Pifithrin-α in the presence of 3 nM [3H]TCDD in HEDG buffer. After incubation on ice with hydroxyapatite for 30 min, HEDG buffer with 0.5% Tween 80 is added. The samples are centrifuged, washed twice, resuspended in 0.2 mL of scintillation fluid, and subjected to scintillation counting. Nonspecific binding is determined using a 150-fold molar excess of TCDF and subtracted from the total binding to obtain the specific binding. The specific binding is reported relative to [3H]TCDD alone[2].