Synonyms: 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
Molecular Formula: C13H12ClN3O3S
Molecular Weight: 325.77
Linear Structural Formula: C13H12ClN3O3S
MDL Number: MFCD30533689
Purity: >=98% (HPLC)
Storage: room temp
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 muM). PF-06282999 effectively inhibits MPO activity in human blood stimulated by LPS ex vivo (IC50 = 1.9 muM) 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 muM/9.36-fold vs.0.8 muM/19.6-fold with rifampin).
Legal Information: Sold for research purposes under agreement from Pfizer Inc