[CAS NO. 1435467-37-0] PF-06282999
PRODUCTS SPECIFICATIONS [1435467-37-0]
DESCRIPTION [1435467-37-0]
Overview
| MDL | MFCD30533689 |
|---|---|
| Molecular Weight | 325.77 |
| Molecular Formula | C13H12ClN3O3S |
| SMILES | O=C(N)CN(C(C1=CC(Cl)=CC=C1OC)=C2)C(NC2=O)=S |
Summary
PF-06282999 is a potent and selective myeloperoxidase inhibitor which is potential useful for the treatment of cardiovascular diseases.
In Vitro
PF-06282999 (Compound 8) is a potent and selective myeloperoxidase inhibitor. The estimated EC 50 for total PF-06282999 concentration in plasma is 3.8 μM, which corresponds well with the IC 50 value obtained in the human whole blood assay of 1.9 μM [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
PF-06282999 is moderately bound to plasma proteins across preclinical species and humans. The blood/plasma ratios for PF-06282999 are 1.1, 1.1, 0.91, 1.2, and 0.94 in mice, rats, dogs, monkeys, and humans, respectively, suggesting that PF-06282999 is equally distributed into plasma and red blood cells [1] . The in vivo pharmacokinetics of PF-06282999 are examined in greater detail in mice, rats, dogs, and monkeys, wherein it is demonstrated to have low CLp in mice (10.1 mL/min/kg), dogs (3.39 mL/min/kg), monkeys (10.3 mL/min/kg) and moderate CLp in rats (41.8 mL/min/kg). The terminal plasma elimination half-lives (t1/2) range from 0.75 to 3.3 h in the four species. Approximately 26-32% of the iv dose of PF-06282999 is excreted in the unchanged form in rat, dog, and monkey urine, wherein it is also shown that it is well distributed with steady state distribution volumes (Vdss) ranging from 0.5-2.1 L/kg in mice, rats, dogs, and monkeys. Following oral administration, PF-06282999 is rapidly (Tmax=0.78-1.70 h) and well absorbed in mice, rats, dogs, and monkeys with oral bioavailability values of 100%, 86%, 75%, and 76%, respectively [2] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01626976 | Pfizer |
Healthy
|
June 2012 | Phase 1 |
| NCT01707082 | Pfizer |
Healthy
|
October 2012 | Phase 1 |
| NCT01965600 | Pfizer |
Healthy
|
March 2014 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 306.97 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 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 |
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
