PF-04957325 is a highly potent and selective PDE8 inhibitor, with IC₅₀s of 0.7 nM and 0.3 nM for PDE8A and PDE8B, respectively.

IC50: 0.7 nM (PDE8A), less than 0.3 nM (PDE8B)^[1]

PF-04957325 is over two orders of magnitude less efficient than PICL in suppressing polyclonal Teff cell proliferation, and shows no effect on cytokine gene expression in these cells, despite its robust effect on T cell adhesion^[1]. PF-04957325 is a selective PDE8 inhibitor and inhibits breast cancer cell migration^[2]. PF-04957325 greatly potentiates steroidogenesis in WT adrenal cells. PF-04957325 shows a reported IC₅₀ of 0.7 nM against PDE8A, 0.2 nM against PDE8B, and > 1.5 μM against all other PDE isoforms^[3]. PF-04957325 treatment of WT Leydig cells or MA10 cells increases steroid production but has no effect in PDE8A (-/-)/B(-/-) double-knockout cells, confirming the selectivity of the drug. Moreover, under basal conditions, cotreatment with PF-04957325 plus rolipram, a PDE4-selective inhibitor, synergistically potentiates steroid production^[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

400.38

C₁₄H₁₅F₃N₈OS

1305115-80-3

Room temperature in continental US; may vary elsewhere.

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

In Vitro: 

DMSO : ≥ 100 mg/mL (249.76 mM)

* “≥” means soluble, but saturation unknown.

*

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, 6 months; -20°C, 1 month。-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。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

  Solubility: ≥ 2.5 mg/mL (6.24 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.24 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

• 2.

  请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

  Solubility: ≥ 2.5 mg/mL (6.24 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.24 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

  将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
• 3.

  请依序添加每种溶剂： 10% DMSO    90% corn oil

  Solubility: ≥ 2.5 mg/mL (6.24 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (6.24 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

• [1]. Vang AG, et al. Differential Expression and Function of PDE8 and PDE4 in Effector T cells: Implications for PDE8 as a Drug Target in Inflammation. Front Pharmacol. 2016 Aug 23;7:259.

  [2]. Dong H, et al. Inhibition of breast cancer cell migration by activation of cAMP signaling. Breast Cancer Res Treat. 2015 Jul;152(1):17-28.

  [3]. Tsai LC, et al. Regulation of adrenal steroidogenesis by the high-affinity phosphodiesterase 8 family. Horm Metab Res. 2012 Sep;44(10):790-4.

  [4]. Shimizu-Albergine M, et al. cAMP-specific phosphodiesterases 8A and 8B, essential regulators of Leydig cell steroidogenesis. Mol Pharmacol. 2012 Apr;81(4):556-66.

Breast cancer cells are in a total volume of 0.1 mL of fresh medium containing the test reagents or vehicle (PF-04957325). Following incubation at 37°C for 72 h, 20 μL of a combined solution of MTS (2 mg/mL)/PMS (0.92 mg/mL) (20:1, mixed immediately before use) is added to each well, and the plates incubated for an additional 2 h at 37°C, protected from light, following which the absorbency of the formazan product formed is determined at 492 nm using a microtiter plate reader. All reagents tested are dissolved in DMSO and diluted into the cell culture medium^[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

• [1]. Vang AG, et al. Differential Expression and Function of PDE8 and PDE4 in Effector T cells: Implications for PDE8 as a Drug Target in Inflammation. Front Pharmacol. 2016 Aug 23;7:259.

  [2]. Dong H, et al. Inhibition of breast cancer cell migration by activation of cAMP signaling. Breast Cancer Res Treat. 2015 Jul;152(1):17-28.

  [3]. Tsai LC, et al. Regulation of adrenal steroidogenesis by the high-affinity phosphodiesterase 8 family. Horm Metab Res. 2012 Sep;44(10):790-4.

  [4]. Shimizu-Albergine M, et al. cAMP-specific phosphodiesterases 8A and 8B, essential regulators of Leydig cell steroidogenesis. Mol Pharmacol. 2012 Apr;81(4):556-66.