β-Lapachone

IDO1:0.44 μM

Beta-lapachone (50 mg/kg) 的处理在人类卵巢癌异种移植小鼠模型中显著抑制体内肿瘤生长，且与taxol联合使用可协同诱导凋亡。[6] 在正常及糖尿病(db/db)小鼠中，beta-lapachone的治疗相比于仅用载体的治疗可加速愈合过程。[3]

Beta-Lapachone通过剂量依赖性方式抑制由DNA拓扑异构酶I引起的DNA松弛。[1] 对Beta-Lapachone（100 nM或更高浓度）的处理导致与DMSO对照相比，Topo I DNA解旋活性的抑制率超过95%。Beta-Lapachone（1-5 μM）通过锁定Topo I到DNA上并阻止复制叉移动，导致HL-60和三种人类前列腺癌细胞（DU-145, PC-3, 和LNCaP）的细胞周期在G0/G1阶段停滞并诱导细胞凋亡。[2] Beta-Lapachone促进小鼠3T3成纤维细胞和人类内皮EAhy926细胞通过不同的MAPK信号途径迁移，从而在体外加速刮擦伤口的愈合。[3] 此外，Beta-Lapachone通过不竞争性抑制作用抑制纯化的重组IDO1活性，IC50为0.44 μM；且Beta-Lapachone还展示出具有IC50为1.0 μM的高效细胞内IDO1抑制活性，该活性部分依赖于NQO1的生物转化。[4] Beta-Lapachone通过NQO1依赖性的活性氧（ROS）生成和PARP1过度激活诱导NQO1+癌细胞的程序性坏死。[5]

Ethanol:12.1 mg/mL (50 mM);DMSO:50 mg/mL (206.38 mM)

IC50 calculations for each cell line are determined by DNA amount (IS) and anchorage-dependent colony formation (CF) assays. For the CF assay, cells are seeded at 500 viable cells/well in 6-well plates and incubated overnight, then treated with equal volumes of media containing beta-lapachone at final concentrations ranging from 0.005 to 50 μM in half-log increments (controls were treated with 0.25% DMSO, equivalent to the highest dose of beta-lapachonc used) for 4 hour or for continuous 12-hour exposures. Plates (3 wells/condition) are stained with crystal violet, and colonies of >50 normal-appearing cells are enumerated. IC50 values for various cells are calculated using drug doses with numbers of colonies surrounding 50% of control. For DNA assays, plates are harvested for IC50 determinations 8 days after treatment using a CytoFluor 2350 fluorescence measurement system. Six-well samplings are included in the calculation of DNA fluor units for each dose. A graph of beta-lapachone dose versus percentage control DNA in fluor units is used to calculate each IC50. All experiments are repeated at least twice, each in duplicate. (Only for Reference)