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PF-2545920

现货
Catalog No.
A4325
PDE10A的有效选择性抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,400.00
现货
5mg
¥ 1,890.00
现货
10mg
¥ 2,590.00
现货
50mg
¥ 6,790.00
现货
200mg
¥ 18,690.00
现货

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Background

PF-2545920 is an inhibitor of phosphodiesterase 10A (PDE10A) with IC50 value of 0.37nM [1].

PDE10A is highly expressed in the medium spiny neurons of the striatum and regulates both cGMP and cAMP. The PDE10A inhibitors are believed to regulate cyclic nucleotide signaling in the cortices-triatothalamic circuit. Previous inhibitors of PDE have potential therapeutic utility but also have potential safety risks due to off-target PDE inhibition. Thereby PF-2545920 is developed as a more selective inhibitor. PF-2545920 is shown to be efficacious both in vitro and in vivo with improved penetration in CNS. It has excellent in vivo efficacy in neurochemical elevation of cyclic nucleotides and in models predictive of antipsychotic activity. Administration of PF-2545920 to mice can cause increase in striatal cGMP with the minimal effective dose at about 1mg/kg [1].

References:
[1] Verhoest PR, Chapin DS, Corman M, Fonseca K, Harms JF, Hou X, Marr ES, Menniti FS, Nelson F, O'Connor R, Pandit J, Proulx-Lafrance C, Schmidt AW, Schmidt CJ, Suiciak JA, Liras S. Discovery of a novel class of phosphodiesterase 10A inhibitors and identification of clinical candidate 2-[4-(1-methyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-phenoxymethyl]-quinoline (PF-2545920) for the treatment of schizophrenia. J Med Chem. 2009 Aug 27;52(16):5188-96.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt392.45
Cas No.1292799-56-4
FormulaC25H20N4O
Solubility≥19.35 mg/mL in DMSO, ≥99.8 mg/mL in EtOH, <2.11 mg/mL in H2O
Chemical Name2-[[4-(1-methyl-4-pyridin-4-ylpyrazol-3-yl)phenoxy]methyl]quinoline
SDFDownload SDF
Canonical SMILESCN1C=C(C(=N1)C2=CC=C(C=C2)OCC3=NC4=CC=CC=C4C=C3)C5=CC=NC=C5
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

大鼠纹状体细胞

溶解方法

在DMSO中的溶解度> 19.35 mg/ml。为了获得更高浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

1μM在30℃下孵育30分钟

应用

PF-2545920的生化特征表明,PF-2545920能够调节多巴胺D1直接和D2间接纹状体通路,并调节纹状体中一系列谷氨酸受体亚型的磷酸化状态。 令人惊奇的是,研究发现PDE10A抑制可以增加细胞表面(+/-)-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸受体GluR1亚基残基丝氨酸845处的磷酸化。

动物实验 [1]:

动物模型

雄性CF-1小鼠或者SD大鼠

剂量

1-30 mg/kg,腹腔注射

应用

PF-2545920在一系列抗精神病药物模型中起作用,它可以拮抗阿朴吗啡诱导的小鼠爬行、抑制大鼠和小鼠中的条件回避反应,并阻断N-甲基-D-天冬氨酸拮抗剂诱导的大鼠声学惊恐反应的前脉冲抑制缺陷。在改善小鼠基线感觉门控的同时,所有这些都进一步验证了以前报告的观察结果。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Grauer SM, et al. Phosphodiesterase 10A inhibitor activity in preclinical models of the positive, cognitive, and negative symptoms of schizophrenia. J Pharmacol Exp Ther, 2009, 331(2), 574-590.

生物活性

Description PF-2545920 is a potent and selective inhibitor of phosphodiesterase 10A (PDE10A) with IC50 value of 0.37 nM.
Targets PDE10A          
IC50 0.37 nM          

质量控制

化学结构

PF-2545920