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Purity: ≥98%
PF-1355 (also known as PF-06281355), a 2-thiouracil analog, is a novel, potent, selective and orally bioavailable mechanism-based MPO inhibitor used for treatment of vasculitic diseases. MPO is a critical mediator of vasculitis in mouse disease models. MPO has been associated with vasculitis, disseminated vascular inflammation typically involving pulmonary and renal microvasculature and often resulting in critical consequences. MPO contributes to vascular injury by 1) catabolizing nitric oxide, impairing vasomotor function; 2) causing oxidative damage to lipoproteins and endothelial cells, leading to atherosclerosis; and 3) stimulating formation of neutrophil extracellular traps, resulting in vessel occlusion and thrombosis. A pharmacokinetic/pharmacodynamic response model of PF-1355 exposure in relation with MPO activity was derived from mouse peritonitis. The contribution of MPO activity to vasculitis was then examined in an immune complex model of pulmonary disease. Oral administration of PF-1355 reduced plasma MPO activity, vascular edema, neutrophil recruitment, and elevated circulating cytokines. In a model of anti-glomerular basement membrane disease, formerly known as Goodpasture disease, albuminuria and chronic renal dysfunction were completely suppressed by PF-1355treatment. This study shows that MPO activity is critical in driving immune complex vasculitis and provides confidence in testing the hypothesis that MPO inhibition will provide benefit in treating human vasculitic diseases.
ln Vitro |
PF-1355 demonstrated a dose-dependent reduction in MPO activity in human neutrophils activated with phorbol ester (EC50 = 1.47 μM) and in residual MPO activity in human blood treated with lipopolysaccharide (EC50 = 2.03 μM) [1].
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ln Vivo |
By reducing plasma MPO activity, angioedema, neutrophil recruitment, and increasing circulating cytokines, PF-1355 is administered orally. Treatment with PF-1355 completely suppressed proteinuria and chronic renal impairment in a model of glomerular basement membrane disease (previously known as Goodpasture's disease) [1].
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References |
[1]. Zheng W, et al. PF-1355, a mechanism-based myeloperoxidase inhibitor, prevents immune complex vasculitis and anti-glomerular basement membrane glomerulonephritis. J Pharmacol Exp Ther. 2015 May;353(2):288-98
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Molecular Formula |
C14H15N3O4S
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Molecular Weight |
321.3516
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CAS # |
1435467-38-1
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SMILES |
O=C(N)CN(C(N1)=S)C(C2=CC(OC)=CC=C2OC)=CC1=O
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InChi Key |
LJBUZOGABRDGBR-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C14H15N3O4S/c1-20-8-3-4-11(21-2)9(5-8)10-6-13(19)16-14(22)17(10)7-12(15)18/h3-6H,7H2,1-2H3,(H2,15,18)(H,16,19,22)
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Chemical Name |
2-(6-(2,5-Dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide
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Synonyms |
PF-1355; PF 1355; PF1355; PF-06281355; PF 06281355; PF06281355;
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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 : ~50 mg/mL (~155.59 mM)
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Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 3.1119 mL | 15.5594 mL | 31.1187 mL | |
5 mM | 0.6224 mL | 3.1119 mL | 6.2237 mL | |
10 mM | 0.3112 mL | 1.5559 mL | 3.1119 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.
Determination of potency and reversibility of PF-1355 for MPO inhibition.J Pharmacol Exp Ther.2015 May;353(2):288-98. th> |
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PF-1355 and MPO deficiency protects in immune complex–induced pulmonary vasculitis.J Pharmacol Exp Ther.2015 May;353(2):288-98. Establishing a pharmacokinetic/pharmacodynamic relationship between plasma [PF-1355] and MPO inhibition in a mouse peritonitis model. td> |
MPO activity is essential for disease induction in a model of anti-GBM glomerulonephritis. td> |