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Purity: ≥98%
PF-04957325 (PF04957325) is a novel, highly potent and selective PDE8 inhibitor with important biological activity. It has IC50s of 0.7 nM and 0.3 nM for PDE8A and PDE8B, respectively. PF-04957325 suppresses T cell adhesion to endothelial cells. Despite its robust effect on T cell adhesion, PF-04957325 was over two orders of magnitude less efficient than PICL in suppressing polyclonal Teff cell proliferation, and showed no effect on cytokine gene expression in these cells. More importantly, PDE8 inhibition did not suppress proliferation and cytokine production of myelin-antigen reactive proinflammatory Teff cells in vivo and in vitro. Thus, targeting PDE8 through PF-04957325 selectively regulates Teff cell interactions with endothelial cells without marked immunosuppression of proliferation, while PDE4 inhibition has partially opposing effects. Collectively, our data identify PF-04957325 as a novel function-specific tool for the suppression of Teff cell adhesion and indicate that PDE4 and PDE8 play unique and non-redundant roles in the control of Teff cell functions.
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| ln Vitro |
PF-04957325 has a strong effect on T cell adhesion, but it is more than two orders of magnitude less effective than PICL at inhibiting the proliferation of polyclonal Teff cells. Additionally, it has no effect on the expression of cytokine genes in these cells[1]. A selective PDE8 inhibitor, PF-04957325 prevents the migration of breast cancer cells[2]. In WT adrenal cells, PF-04957325 significantly enhances steroidogenesis. The IC50 values of PF-04957325 are 0.7 nM for PDE8A, 0.2 nM for PDE8B, and > 1.5 μM for all other PDE isoforms [3]. The selective drug PF-04957325 increases steroid production in WT Leydig cells or MA10 cells, but has no effect in PDE8A (-/-)/B(-/-) double-knockout cells. Additionally, cotreatment with PDE4-selective inhibitor rolipram and PF-04957325 enhances steroid production under basal conditions[4].
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| References |
[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 |
| Molecular Formula |
C14H15F3N8OS
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| Molecular Weight |
400.3821
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| CAS # |
1305115-80-3
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| SMILES |
NC1=C(N=NN2C[C@H]3CN(CC4=NC=CS4)CCO3)C2=NC(C(F)(F)F)=N1
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| Synonyms |
PF-04957325; PF 04957325; PF04957325
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~249.76 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.24 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.24 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.24 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4976 mL | 12.4881 mL | 24.9763 mL | |
| 5 mM | 0.4995 mL | 2.4976 mL | 4.9953 mL | |
| 10 mM | 0.2498 mL | 1.2488 mL | 2.4976 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Inhibiting PDE8 suppresses Teff cell adhesion to endothelial cells and is reversed by PDE4 inhibition.Front Pharmacol.2016 Aug 23;7:259. |
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 Selective inhibition of Teff cell proliferation by PDE4 inhibitionin vitro. Proliferation of purified CD4+CD25−Teff cells exposed to PDE inhibitors.Front Pharmacol.2016 Aug 23;7:259. |
 PF-04957325 does not suppress T cell proliferation in response to MOG35−55ex vivoandin vitro. |
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