体外研究
Brequinar reduces virus progeny production by >90%, with EC
50
of 17 nM. Brequinar (5 μM) also inhibits other orthopoxviruses, and blocks virus DNA replication. Brequinar does not affect virus early gene expression, but has a severe effect on the late stage of the virus cycle. Brequinar reduces the level of envelope protein production and the viral titer in a dose-dependent manner, with EC
50
of 78 nM in the CFI assay. Brequinar (5 μM) inhibits viral RNA synthesis. Brequinar has antiviral effect, but the effect is reversed by pyrimidine. Brequinar-resistant viruses can be selected in cell culture. Brequinar (5 μM) suppresses the luciferase activities from both the WT and NS5 mutant replicons. Brequinar sodium effectively prevents the increase in PyNTP levels with an IC
50
of 0.26 μM. Brequinar sodium effectively inhibits cell proliferation with an IC
50
of 0.26 μM. Brequinar sodium inhibits autophosphorylation of p56
lck
with IC
50
of 70 μM; inhibition is 39, 41, and 60% for 25, 50, and 100 μM Brequinar sodium, respectively. Brequinar sodium also inhibits the phosphorylation by p56
lck
of the exogenous substrate, histone 2B, with an IC
50
of 70 μM; inhibition is 10, 43, 59, and 86% for 25, 50, 100, and 200 μM Brequinar sodium, respectively. Brequinar sodium inhibits autophosphorylation of p59
fyn
with an IC
50
of 105 μM; inhibition is 0, 17, 48, and 65% for 25, 50, 100, and 200 μM Brequinar sodium, respectively. Brequinar sodium also inhibits the phosphorylation by p59
fyn
of histone 2B with an IC
50
of 20 μM; inhibition is 26, 54, 79, 83, and 84% for 10, 25, 50, 100, and 200 μM Brequinar sodium, respectively.
PSA
50.19 Ų
储存条件
0-10°C;避免加热
外观
White to Light yellow powder to crystal
密度
1.3±0.1 g/cm³
折射率
1.645
沸点
550.9±50.0 °C (760 mmHg)
溶解度
DMSO:25.9 mg/mL (最大浓度);70.0 mM (最大浓度)
熔点
317 °C
精确质量
375.107086
蒸汽压
0.0±1.6 mmHg (25 °C)
酸度系数(pKa)
4.45 (H₂O, t=RT, I=0.10, Uncertain)
闪点
287.0±30.1 °C
体内研究
Brequinar sodium-treated (10-20 mg/kg/day) mice has a 31% reduction in percentage of packed cell volume compared with untreated BALB/c mice. Brequinar sodium reduces UTP and CTP levels in bone marrow cells by 30 and 25%, respectively. Brequinar sodium (10-20 mg/kg/day) in combination with uridine (1000-2000 mg/kg/day) prevents anemia, and the hematocrits remain at levels (61-63%) comparable with those of untreated controls.
