PF-04957325是一种高效的PDE8选择性抑制剂，其抑制PDE8A和PDE8B的IC50分别为0.7nM和0.3nM。
Cas No.:1305115-80-3
Sample solution is provided at 25 µL, 10mM.
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PF-04957325 is a kind of highly potent PDE8-selective inhibitor and the values of IC50 for PDE8A and PDE8B are 0.7nM and 0.3nM, respectively [1].
PF-04957325 (0.1, 1μM; 45min) inhibited T cell adhere to endothelial cells [2]. PF-04957325 (0.01 ~1000nM) increased concentrations of cAMP in a concentration-dependent manner in HASM cells [3].
PF-04957325 (0.1, 1mg/kg; 21d; i.g.) downregulated the expression levels of IL-1β, IL-6 and COX-2 in AβO-induced alzheimer’s disease (AD) C57BL/6J mice; PF-04957325 (1mg/kg; 21d; i.g.) increased the expression of CD206 and Arg-1 with a significant effect in AβO-induced AD C57BL/6J mice [4]. PF-04957325 (10mg/kg; 4d; bid; s.c.) showed significant reductions in the number of infiltrates in the brain meninges and spinal cord in experimental autoimmune encephalomyelitis (EAE) C57BL/6 mice [5].
References:
[1] Vang A G, Ben-Sasson S Z, Dong H, et al. PDE8 regulates rapid Teff cell adhesion and proliferation independent of ICER [J]. PLoS one, 2010, 5(8): e12011.
[2] Vang A G, Basole C, Dong H, et al. Differential expression and function of PDE8 and PDE4 in effector T cells: implications for PDE8 as a drug target in inflammation [J]. Frontiers in pharmacology, 2016, 7: 259.
[3] Johnstone T B, Smith K H, Koziol-White C J, et al. PDE8 is expressed in human airway smooth muscle and selectively regulates cAMP signaling by β(2)-adrenergic receptors and adenylyl cyclase 6 [J]. American journal of respiratory cell and molecular biology, 2018, 58(4): 530-541.
[4] Guo T Y, Zhang M, Lv Y L, et al. Cognitive improvement effects of PF-04957325, a phosphodiesterase-8 inhibitor, in mouse models of Alzheimer's disease via modulating neuroinflammation [J]. The international journal of neuropsychopharmacology, 2025, 28(5): pyaf028.
[5] Basole C P, Nguyen R K, Lamothe K, et al. Treatment of experimental autoimmune encephalomyelitis with an inhibitor of phosphodiesterase-8 (PDE8) [J]. Cells, 2022, 11(4): 660.
PF-04957325是一种高效的PDE8选择性抑制剂，其抑制PDE8A和PDE8B的IC50分别为0.7nM和0.3nM[1]。
PF-04957325（0.1和1μM；45min）可以抑制T细胞与内皮细胞的黏附[2]。PF-04957325（0.01 ~1000nM）以浓度依赖的方式增加HASM细胞内的cAMP浓度[3]。
PF-04957325（0.1、1mg/kg；21d；i.g.）下调了由AβO引发的阿尔茨海默症C57BL/6J小鼠模型体内IL-1β、IL-6和COX-2的表达水平；PF-04957325（1mg/kg；21d；i.g.）对增加由AβO引发的阿尔茨海默症C57BL/6J小鼠模型的CD206和Arg-1的表达有显著作用[4]。PF-04957325（1mg/kg；4d；bid；s.c.）显著减少了实验性自身免疫性脑脊髓炎C57BL/6小鼠模型的脑膜和脊髓中的浸润物数量[5]。
| Cell experiment [1]: | |
Cell lines | Murine brain endothelium-derived cell line bEnd.3 |
Preparation Method | PF-04957325 was added to bEnd.3 cells for the last 45min of incubation. T cell blasts or Teff cells were labeled with Calcein AM and then were incubated on bEnd.3 cells. Calcein AM labeled T cell blasts or Teff cells were used as positive controls. |
Reaction Conditions | 0.1 and 1μM; 45min |
Applications | PF-04957325 suppressed T cell adhesion to endothelial cells. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6J mice |
Preparation Method | The alzheimer’s disease (AD) mouse models were established by microinjecting AβO into the hippocampus. The mice were administered by gavage with PF-04957325 at the dose of 0.1 or 1mg/kg or its vehicle for consecutive 21d after 3d of AβO stimulation. The inflammatory factors were determined using Mouse Quantikine ELISA kits. |
Dosage form | 0.1, 1mg/kg; 21d; i.g. |
Applications | PF-04957325 downregulated the expression levels of IL-1β, IL-6, and COX-2 in AβO-induced AD model mice. |
References: | |
| Cas No. | 1305115-80-3 | SDF | |
| Canonical SMILES | NC1=C(N=NN2C[C@H]3CN(CC4=NC=CS4)CCO3)C2=NC(C(F)(F)F)=N1 | ||
| 分子式 | C14H15F3N8OS | 分子量 | 400.38 |
| 溶解度 | DMSO : 9.9 mg/mL (24.73 mM) | 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 | 2.4976 mL | 12.4881 mL | 24.9763 mL |
| 5 mM | 499.5 μL | 2.4976 mL | 4.9953 mL |
| 10 mM | 249.8 μL | 1.2488 mL | 2.4976 mL |
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动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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工作液浓度： mg/ml；
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2.
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- Purity: >99.50% Appearance: A solid
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