| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| 1g |
|
||
| Other Sizes |
|
Purity: ≥98%
PF-06282999 is a novel, potent and selective myeloperoxidase (MPO) inhibitor with the potential for the treatment of cardiovascular diseases. Robust inhibition of plasma MPO activity was demonstrated with PF-06282999 upon oral administration to lipopolysaccharide-treated cynomolgus monkeys. On the basis of its pharmacological and pharmacokinetic profile, PF-06282999 has been advanced to first-in-human pharmacokinetic and safety studies. Myeloperoxidase (MPO) is a heme peroxidase that catalyzes the production of hypochlorous acid. Clinical evidence suggests a causal role for MPO in various autoimmune and inflammatory disorders including vasculitis and cardiovascular and Parkinson's diseases, implying that MPO inhibitors may represent a therapeutic treatment option.
| ln Vitro |
PF-06282999 (Compound 8) is a strong and specific myeloperoxidase inhibitor. The IC50 value of 1.9 μM found in human whole blood testing is in good agreement with the expected EC50 value of 3.8 μM for the total concentration of PF-06282999 in plasma [2].
|
|---|---|
| ln Vivo |
In humans and preclinical animals, PF-06282999 is moderately bound to plasma proteins. Mice, rats, dogs, monkeys, and humans had blood/plasma ratios of PF-06282999 of 1.1, 1.1, 0.91, 1.2, and 0.94, respectively, suggesting that PF-06282999 is dispersed equally in plasma and red blood cells [1]. More research was done on the in vivo pharmacokinetics of PF-06282999 in mice, rats, dogs, and monkeys. The results showed that it was medium with low CLp in the monkeys (10.3 mL/min/kg), and moderate with the rats (41.8 mL/min/kg). The four species' terminal plasma elimination half-lives (t1/2) varied from 0.75 to 3.3 hours. The urine of rats, dogs, and monkeys excretes about 26-32% of an intravenous dose of PF-06282999 unaltered. It has also been demonstrated to be well dispersed in these animals, with a steady-state volume of distribution (Vdss) in the range of 0.5 - mouse, rat, and 2.1 L/kg in dogs and monkeys. In mice, rats, dogs, and monkeys, oral administration of PF-06282999 results in rapid (Tmax=0.78-1.70 h) and well-absorbed drug with oral bioavailability values of 100%, 86%, 75%, and 76%, respectively [2].
|
| References |
[1]. Dong JQ, et al. Pharmacokinetics and Disposition of the Thiouracil Derivative PF-06282999, an Orally Bioavailable, Irreversible Inactivator of Myeloperoxidase Enzyme, Across Animals and Humans. Drug Metab Dispos. 2016 Feb;44(2):209-19.
[2]. Ruggeri RB, et al. Discovery of 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide (PF-06282999): A Highly Selective Mechanism-Based Myeloperoxidase Inhibitor for the Treatment of Cardiovascular Diseases. J Med Chem. 20 |
| Molecular Formula |
C13H12CLN3O3S
|
|---|---|
| Molecular Weight |
325.77
|
| CAS # |
1435467-37-0
|
| SMILES |
O=C(N)CN(C(C1=CC(Cl)=CC=C1OC)=C2)C(NC2=O)=S
|
| Synonyms |
PF-06282999; PF 06282999; PF06282999
|
| 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)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~306.97 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (7.67 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
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 (7.67 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (7.67 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0697 mL | 15.3483 mL | 30.6965 mL | |
| 5 mM | 0.6139 mL | 3.0697 mL | 6.1393 mL | |
| 10 mM | 0.3070 mL | 1.5348 mL | 3.0697 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA