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PZ0375

Sigma-Aldrich

PF-06282999

≥98% (HPLC)

Synonym(s):

2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide, 6-(5-Chloro-2-methoxyphenyl)-3,4-dihydro-4-oxo-2-thioxo-1(2H)-pyrimidineacetamide, PF 06282999, PF06282999

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About This Item

Empirical Formula (Hill Notation):
C13H12ClN3O3S
CAS Number:
1435467-37-0
Molecular Weight:
325.77
MDL number:
MFCD30533689
UNSPSC Code:
51111800
NACRES:
NA.77

assay

≥98% (HPLC)

form

powder

color

white to beige

solubility

DMSO: 2 mg/mL, clear

storage temp.

room temp

SMILES string

O=C(N)CN(C(N1)=S)C(C2=CC(Cl)=CC=C2OC)=CC1=O

Biochem/physiol Actions

PF-06282999 is an orally active thiouracil class myeloperoxidase (MPO) suicide substrate (kinact/KI = 11600 M-1s-1) that targets MPO heme group for mechanism-based irreversible inactivation wtih high selectivity over thyroid peroxidase (TPO kinact/KI <3 M-1s-1) and heme-containing cytochrome P450 (CYP) isoforms (IC50 >100 μM). PF-06282999 effectively inhibits MPO activity in human blood stimulated by LPS ex vivo (IC50 = 1.9 μM) and in blood of LPS-treated cynomolgus monkeys in vivo (5-80 mg/kg p.o. 1hr post LPS i.v.) with good pharmacokinetics and oral availability (100%/86%/75%/76% in mice/rats/dogs/monkeys). PF-06282999 also exhibits weak PXR activating activity (EC50/Emax = 279 μM/9.36-fold vs.0.8 μM/19.6-fold with rifampin).

wgk_germany

WGK 3

flash_point_f

Not applicable

flash_point_c

Not applicable

Certificates of Analysis (COA)

Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.

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Roger B Ruggeri et al.
Journal of medicinal chemistry, 58(21), 8513-8528 (2015-10-29)
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
Jennifer Q Dong et al.
Drug metabolism and disposition: the biological fate of chemicals, 45(5), 501-511 (2017-03-04)
The propensity for CYP3A4 induction by 2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2
Jennifer Q Dong et al.
Drug metabolism and disposition: the biological fate of chemicals, 44(2), 209-219 (2015-11-27)
The thiouracil derivative PF-06282999 [2-(6-(5-chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide] is an irreversible inactivator of myeloperoxidase and is currently in clinical trials for the potential treatment of cardiovascular diseases. Concerns over idiosyncratic toxicity arising from bioactivation of the thiouracil motif to reactive species in the
Jamie E Moscovitz et al.
Xenobiotica; the fate of foreign compounds in biological systems, 48(7), 647-655 (2017-07-08)
1. 2-(6-(5-Chloro-2-methoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl) acetamide (PF-06282999) is a member of the thiouracil class of irreversible inactivators of human myeloperoxidase enzyme and a candidate for the treatment of cardiovascular disease. PF-06282999 is an inducer of CYP3A4 mRNA and midazolam-1'-hydroxylase activity in human hepatocytes

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