10058-F4 是一种细胞渗透性噻唑烷酮，可特异性抑制 c-Myc-Max 相互作用并防止 c-Myc 靶基因表达的反式激活；诱导细胞周期停滞和凋亡。

10058-F4 is a cell-permeable thiazolidinone that specifically inhibits the c-Myc-Max interaction and prevents transactivation of c-Myc target gene expression; induces cell-cycle arrest and apoptosis.

10058-F4在脂肪、肺、肝脏和肾脏中含量最高.10058-F4的肿瘤峰值浓度至少比血浆峰值浓度低10倍.10058-F4的分布容积>200 ml/kg,终端半衰期约为1 h.10058-F4（20/30 mg/kg,i.v.）对小鼠肿瘤生长无明显抑制作用.10058-F4（i.v.）在5 min时达到血浆峰值（300 μM）,在6 h时浓度低于检测下限.

10058-F4使AML细胞停滞在G0/G1期,使c-Myc的表达下调、CDK抑制剂p21和p27上调。同时,其通过激活线粒体途径诱导细胞凋亡,出现Bcl-2下调,Bax上调,胞浆内细胞色素C释放,及caspase3/7/9裂解。此外,10058-F4可能通过激活多种转录因子从而诱导骨髓细胞分化。相似地,10058-F4可诱导原代AML细胞凋亡和分化。10058-F4使c-Myc蛋白水平降低并抑制HepG2细胞增殖,可能与上调细胞周期蛋白依赖性激酶抑制剂p21WAF1及降低细胞内[α]-甲胎蛋白的水平有关。10058-F4还可在转录水平使人端粒酶逆转录酶下调。除抑制HepG2细胞增殖外,10058-F4还增强其对常规化疗药物,阿霉素, 5-氟尿嘧啶和顺铂的敏感性。

Cells, plated in 96-well plates (105/mL for cell lines and 5 × 105/mL for primary leukemic cells), are treated in triplicate with indicated concentrations of 10058-F4. At various time points, 20 μL 5 mg/mL MTT is added to each well. After incubation at 37°C for 3 hours, the MTT medium is removed and 100 μL DMSO lysis buffer is added. The number of viable cells is assessed by the percentage of absorbance of treated cells relative to that of solvent controls, using 570-nm wavelength on a spectrophotometer.(Only for Reference)

403811-55-2

C12H11NOS2

249.35

c-Myc Inhibitor

DMSO:24.9 mg/mL (100 mM)
H2O:<1 mgml
Ethanol:5 mg/mL (20 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years