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WWL 70

现货
Catalog No.
A8891
α/β水解酶域6抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 1,100.00
Ship with 10-15 days
5mg
¥ 800.00
Ship with 10-15 days
10mg
¥ 1,200.00
Ship with 10-15 days
50mg
¥ 4,800.00
Ship with 10-15 days
2000mg
¥ 65,000.00
Ship with 10-15 days

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Background

WWL 70 is a potent inhibitor of α/β-hydrolase domain 6 (ABHD6) with IC50 value of 70 nM [1].

WWL 70 is an O-aryl group-modified derivative of carbamate 18 which is a lead inhibitor of ABHD6 screened out by a functional proteomic strategy. WWL 70 is about 5-fold more potent than carbamate 18. The improved potency makes no difference in selectivity of WWL 70 and carbamate 18 as measured by competitive ABPP with brain membrane proteome. WWL 70 was selective against ABHD6 over other 27 SH activities except for ABHD10 which showed a significant reduction in activity in WWL 70-treated proteomes. However, WWL 70 had no effect on recombinant ABHD10 at concentration of 100 μM, suggesting that ABHD10 was not a real target [1].

References:
[1] Li W, Blankman J L, Cravatt B F. A functional proteomic strategy to discover inhibitors for uncharacterized hydrolases. Journal of the American Chemical Society, 2007, 129(31): 9594-9595.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt437.49
Cas No.947669-91-2
FormulaC27H23N3O3
Solubility≥14.45mg/mL in DMSO
Chemical Name4'-carbamoyl-[1,1'-biphenyl]-4-yl methyl(3-(pyridin-4-yl)benzyl)carbamate
SDFDownload SDF
Canonical SMILESO=C(N(C)CC1=CC=CC(C2=CC=NC=C2)=C1)OC3=CC=C(C=C3)C4=CC=C(C(N)=O)C=C4
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验: [1]

细胞系

HEK293细胞

制备方法

该化合物在DMSO中的溶解度大于10 mM,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

10 μM,10 min

实验结果

去极化诱导的激发抑制(DSE)是大麻素介导的短期逆行神经元可塑性的主要形式,并且在许多脑区中发现。ABHD6不存在于自激神经元的突触前,ABHD6抑制剂WWL70对自发DSE时间进程没有影响。

动物实验: [1]

动物模型

雄性C57BL/6小鼠, 25–30 g

给药剂量

在TBI后30分钟腹腔注射溶解在1%DMSO的生理盐水中的WWL70(5 mg/kg或10 mg/kg),每天一次,持续时间大于等于7天,具体时间取决于实验设计。

实验结果

WWL70是一种选择性ABHD6抑制剂,改善运动协调和工作记忆性能。WWL70减少皮质中的损伤体积和树突回中的神经变性,它还抑制诱导型一氧化氮合酶和环加氧酶-2的表达,并在TBI后3和7天增强同侧皮质中精氨酸酶-1的表达,表明小胶质细胞/巨噬细胞在治疗后从M1转换到M2表型。在TBI后3和7天的血脑屏障功能障碍显著降低。此外,WWL70的有益效果包括大麻素1型和2型受体的上调和活化,这种效果归因于细胞外信号调节激酶和丝氨酸/苏氨酸蛋白激酶AKT的磷酸化。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

1. Straiker A1, Hu SS, Long JZ et al. Monoacylglycerol lipase limits the duration of endocannabinoid-mediated depolarization-induced suppression of excitation in autaptic hippocampal neurons. Mol Pharmacol. 2009 Dec;76(6):1220-7.

2. Tchantchou F1, Zhang Y. Selective inhibition of alpha/beta-hydrolase domain 6 attenuates neurodegeneration, alleviates blood brain barrier breakdown, and improves functional recovery in a mouse model of traumatic brain injury. J Neurotrauma. 2013 Apr 1;30(7):565-79.

质量控制

化学结构

WWL 70