PF-2545920
(Synonyms: 2-[[4-[1-(甲基-11C)-4-(4-吡啶基)-1H-吡唑-3-基]苯氧基]甲基]喹啉) 目录号 : GC15194
A potent inhibitor of PDE10A
Cas No.:1292799-56-4
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment [1]: | |
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Cell lines |
Rat striatal cells |
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Preparation method |
The solubility of this compound in DMSO is >19.35 mg/ml. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
1 μM for 30 min at 30°C |
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Applications |
Biochemical characterization of PF-2545920 showed that it could modulate both the dopamine D1-direct and D2-indirect striatal pathways and regulate the phosphorylation status of a panel of glutamate receptor subunits in the striatum. It was striking that PDE10A inhibition increased the phosphorylation of the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptor GluR1 subunit at residue serine 845 at the cell surface. |
| Animal experiment [1]: | |
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Animal models |
Male CF-1 mice or Sprague-Dawley rats |
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Dosage form |
1-30 mg/kg, i.p. |
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Application |
PF-2545920 was active in a range of antipsychotic models, antagonizing apomorphine-induced climbing in mice, inhibiting conditioned avoidance responding in both rats and mice, and blocking N-methyl-D-aspartate antagonist-induced deficits in prepulse inhibition of acoustic startle response in rats, while improving baseline sensory gating in mice, all of which strengthen previously reported observations. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
| Cas No. | 1292799-56-4 | SDF | |
| 别名 | 2-[[4-[1-(甲基-11C)-4-(4-吡啶基)-1H-吡唑-3-基]苯氧基]甲基]喹啉 | ||
| 化学名 | 2-[[4-(1-methyl-4-pyridin-4-ylpyrazol-3-yl)phenoxy]methyl]quinoline | ||
| Canonical SMILES | CN1C=C(C(=N1)C2=CC=C(C=C2)OCC3=NC4=CC=CC=C4C=C3)C5=CC=NC=C5 | ||
| 分子式 | C25H20N4O | 分子量 | 392.45 |
| 溶解度 | ≥ 19.35 mg/mL in DMSO, ≥ 99.8 mg/mL in EtOH | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5481 mL | 12.7405 mL | 25.481 mL |
| 5 mM | 0.5096 mL | 2.5481 mL | 5.0962 mL |
| 10 mM | 0.2548 mL | 1.274 mL | 2.5481 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet