WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H522473
CAS#: 1435467-37-0
Description: PF-06282999 is a potent and selective myeloperoxidase Inhibitor which is potential useful for the Treatment of Cardiovascular Diseases. PF-06282999 displayed excellent oral pharmacokinetics in preclinical species and robust irreversible inhibition of plasma MPO activity both in human blood stimulated exogenously and in plasma collected after oral (po) administration to lipopolysaccharide (LPS)-treated cynomolgus monkeys. PF-06282999 has been advanced into first-in-human pharmacokinetics and safety studies.
Hodoodo Cat#: H522473
Name: PF-06282999
CAS#: 1435467-37-0
Chemical Formula: C13H12ClN3O3S
Exact Mass: 325.03
Molecular Weight: 325.770
Elemental Analysis: C, 47.93; H, 3.71; Cl, 10.88; N, 12.90; O, 14.73; S, 9.84
Synonym: PF-06282999; PF06282999; PF06282999.
IUPAC/Chemical Name: 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide
InChi Key: ICYNYWFGIDGBRD-UHFFFAOYSA-N
InChi Code: InChI=1S/C13H12ClN3O3S/c1-20-10-3-2-7(14)4-8(10)9-5-12(19)16-13(21)17(9)6-11(15)18/h2-5H,6H2,1H3,(H2,15,18)(H,16,19,21)
SMILES Code: O=C(N)CN(C(N1)=S)C(C2=CC(Cl)=CC=C2OC)=CC1=O
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | PF-06282999 is a myeloperoxidase inhibitor. |
| In vitro activity: | The potential for induction of CYP3A4 mRNA and enzyme activity was examined in cryopreserved human hepatocytes treated with PF-06282999 at several concentrations (0.3–300 μM). PF-06282999 demonstrated moderate induction of CYP3A4 mRNA levels and midazolam-1’-hydroxylase activity in a dose-dependent fashion in all three donor hepatocytes (Fig. 1). Reference: Drug Metab Dispos. 2017 May;45(5):501-511. https://dmd.aspetjournals.org/content/45/5/501.long |
| In vivo activity: | TBD |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 30.0 | 92.10 |
The following data is based on the product molecular weight 325.77 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Dong JQ, Gosset JR, Fahmi OA, Lin Z, Chabot JR, Terra SG, Le V, Chidsey K, Nouri P, Kim A, Buckbinder L, Kalgutkar AS. Examination of the Human Cytochrome P4503A4 Induction Potential of PF-06282999, an Irreversible Myeloperoxidase Inactivator: Integration of Preclinical, In Silico, and Biomarker Methodologies in the Prediction of the Clinical Outcome. Drug Metab Dispos. 2017 May;45(5):501-511. doi: 10.1124/dmd.116.074476. Epub 2017 Mar 2. PMID: 28254951. |
| In vitro protocol: | 1. Dong JQ, Gosset JR, Fahmi OA, Lin Z, Chabot JR, Terra SG, Le V, Chidsey K, Nouri P, Kim A, Buckbinder L, Kalgutkar AS. Examination of the Human Cytochrome P4503A4 Induction Potential of PF-06282999, an Irreversible Myeloperoxidase Inactivator: Integration of Preclinical, In Silico, and Biomarker Methodologies in the Prediction of the Clinical Outcome. Drug Metab Dispos. 2017 May;45(5):501-511. doi: 10.1124/dmd.116.074476. Epub 2017 Mar 2. PMID: 28254951. |
| In vivo protocol: | TBD |
1: Ruggeri RB, Buckbinder L, Bagley SW, Carpino PA, Conn EL, Dowling MS, Fernando DP, Jiao W, Kung DW, Orr ST, Qi Y, Rocke BN, Smith A, Warmus JS, Zhang Y, Bowles D, Widlicka DW, Eng H, Ryder T, Sharma R, Wolford A, Okerberg C, Walters K, Maurer TS, Zhang Y, Bonin PD, Spath SN, Xing G, Hepworth D, Ahn K, Kalgutkar AS. 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. 2015 Oct 28. [Epubahead of print] PubMed PMID: 26509551.
