1. Metabolic Enzyme/Protease
  2. Glutathione Peroxidase
  3. PF-06282999

PF-06282999 

Cat. No.: HY-19321 Purity: 99.41%
Handling Instructions

PF-06282999 is a potent and selective myeloperoxidase inhibitor which is potential useful for the treatment of cardiovascular diseases.

For research use only. We do not sell to patients.

PF-06282999 Chemical Structure

PF-06282999 Chemical Structure

CAS No. : 1435467-37-0

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 284 In-stock
Estimated Time of Arrival: December 31
1 mg USD 132 In-stock
Estimated Time of Arrival: December 31
5 mg USD 396 In-stock
Estimated Time of Arrival: December 31
10 mg USD 600 In-stock
Estimated Time of Arrival: December 31
25 mg USD 1200 In-stock
Estimated Time of Arrival: December 31
50 mg USD 1800 In-stock
Estimated Time of Arrival: December 31
100 mg USD 2520 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Based on 1 publication(s) in Google Scholar

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Description

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 EC50 for total PF-06282999 concentration in plasma is 3.8 μM, which corresponds well with the IC50 value obtained in the human whole blood assay of 1.9 μM[2].

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].

Clinical Trial
Molecular Weight

325.77

Formula

C₁₃H₁₂ClN₃O₃S

CAS No.

1435467-37-0

SMILES

O=C(N)CN(C(C1=CC(Cl)=CC=C1OC)=C2)C(NC2=O)=S

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
In Vitro: 

DMSO : ≥ 32 mg/mL (98.23 mM)

*"≥" means soluble, but saturation unknown.

Preparing
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
*Please refer to the solubility information to select the appropriate solvent.
References
Kinase Assay
[2]

Test compound is incubated with human whole blood stimulated with bacterial LPS for 4 h, followed by capture of MPO on immobilized anti-MPO antibody coated plates. The captured MPO is washed and residual MPO activity is determined using Amplex Red and H2O2.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

In order to ascertain whether the advances noted in the in vitro and ex vivo assays for candidate thiouracil derivatives translated to effective irreversible inhibition of MPO in vivo, PF-06282999 is also advanced to an in vivo pharmacology study in cynomolgus monkeys using iv endotoxin (LPS) challenge, a classic model of inflammatory leukocyte activation with corresponding MPO activation demonstrated in various species including human. In this randomized crossover study, cynomolgus monkeys are orally administered either vehicle or PF-06282999 (5, 20, and 80 mg/kg) 1 h after iv administration of LPS. Blood is sampled throughout the study and heparinized plasma prepared for MPO activity measurements as well as determination of 8 plasma concentrations. Total MPO is captured using anti-MPO antibody coated plates, and following exchange of plasma for drug-free assay media, the residual activity of the captured MPO is measured using the peroxidation of Amplex Red. A mixed effect sigmoid model is applied to study the relationship between plasma exposure of PF-06282999 and the MPO capture activity at 2 h after dose and 3 h after LPS administration, which corresponds to the peak of MPO activity.

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References

Purity: 99.41%

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Keywords:

PF-06282999PF06282999PF 06282999Glutathione PeroxidaseInhibitorinhibitorinhibit

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PF-06282999
Cat. No.:
HY-19321
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