ML352 is a novel and noncompetitive inhibitor of the presynaptic choline transporter, with Ki of 92 nM.
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描述 | The high-affinity choline transporter (CHT) is the rate-limiting determinant of acetylcholine (ACh) synthesis, yet the transporter remains a largely undeveloped target for the detection and manipulation of synaptic cholinergic signaling. ML352 is a selective CHT inhibitor. ML352 inhibited [3H]choline uptake with high affinity (Ki = 92 ± 2.8 nM). When combined with fixed concentrations of ML352, a concentration-dependent reduction in transport Vmax relative to vehicle-treated control was evident (Vmax 200 nM ML352 = 70.4 ± 5.6%; 800 nM, 30.3 ± 4.2%). Analysis of ML352 inhibitory actions on choline uptake in mouse forebrain synaptosomes yielded similar effects (Vmax 300 nM ML352 = 57.2 ± 3.4%). ML352 demonstrated dose-dependent inhibition of HC-3 binding, well-fit by a single-site inhibition model (r = 0.948) with a Ki of 128.6 ± 15.3 nM, similar to that found in uptake inhibition studies. In support of uptake inhibition findings, a significant reductions in [3H]HC-3 binding Bmax (Bmax 200 nM ML352 = 80.3 ± 3.8%; 800 nM, 48.9 ± 4.1%) was observed. ML352 at saturating concentrations (5 μM) also induced a significant increase in hCHT surface expression (43.4 ± 4.7% of control)[1]. |
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存储液制备 | 1mg | 5mg | 10mg | |
1 mM 5 mM 10 mM |
2.58mL 0.52mL 0.26mL |
12.90mL 2.58mL 1.29mL |
25.81mL 5.16mL 2.58mL |
CAS号 | 1649450-12-3 |
分子式 | C21H29N3O4 |
分子量 | 387.473 |
别名 | |
运输 | 蓝冰 |
存储条件 |
粉末 Sealed in dry,2-8°C 液体 -20°C:3-6个月-80°C:12个月 |
溶解度 |
DMSO: 250 mg/mL(645.21 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO |
动物实验配方 |