布喹那

中文名称:

布喹那

中文同义词:

BREQUINAR 布喹那;布喹钠;布喹那;DIHYDROOROTATE DEHYDROGENASE抑制剂(BREQUINAR);6-氟-2-(2-氟-[1,1-联苯]-4-基)-3-甲基喹啉-4-羧酸

英文名称:

Brequinar

英文同义词:

Brequinar;6-Fluoro-2-(2-fluoro[1,1-biphenyl]-4-yl)-3-methyl-4-quinolinecarboxylic acid;6-fluoro-2-(2-fluorobiphenyl-4-yl)-3-methylquinoline-4-carboxylic acid;6-fluoro-2-(2-fluorobiphenyl-4-yl)-3-Methylquinoline-4-carboxyl;4-Quinolinecarboxylic acid, 6-fluoro-2-(2-fluoro[1,1-biphenyl]-4-yl)-3-Methyl-;6-Fluoro-2-(2-fluoro-[1,1-biphenyl]-4-yl)-3-methylquinoline-4-carboxylic acid;Biphenquinate;BPQ

CAS号:

96187-53-0

分子式:

C23H15F2NO2

分子量:

375.37

EINECS号:

相关类别:

细胞生物学试剂;化工原料;API

Mol文件:

96187-53-0.mol

熔点 

355-357℃ (N,N-dimethylformamide water )

储存条件 

Sealed in dry,2-8°C

酸度系数(pKa)

pKa 4.45(H2O t=RT I=0.10) (Uncertain)

CAS 数据库

96187-53-0

生物活性

Brequinar (NSC 368390, DuP-785)是二氢乳清酸脱氢酶DHODH抑制剂，在体外IC50约为20 nM。

靶点

Target Value DHODH () 20 nM

Target

Value

DHODH ()

20 nM

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.

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.