Sepin-1 is a potent separase inhibitor with an IC50 value of 14.8 µM. Sepin-1 inhibits cell proliferation, migration and wound healing. Sepin-1 decreases the expression of FoxM1 protein and mRNA level. Sepin-1 shows anti-tumor activity[1][2].
Sepin-1 (0, 20, 40 µM; 24 h) 抑制细胞迁移和伤口愈合，并引起 DNA 损伤[1]。
Sepin-1 (0, 10, 20, 40 µM; 24 h) 以剂量依赖性方式降低 FoxM1 蛋白和 mRNA 水平的表达[1]。
Sepin-1 (0, 10, 20, 40 µM; 24 h) 抑制 Plk1、Cdk1、pericentrin、Aurora 和 Lamin B1 蛋白水平的表达[1]。
Cell Proliferation Assay[1]
| Cell Line: | BT-474, MCF7, MDA-MB-231, MDA-MB-468 cells |
| Concentration: | 0-64 µM |
| Incubation Time: | 3 days |
| Result: | Inhibited cell growth with EC50s of 18.03, 17.66, 27.33, 27.92 µM for BT-474, MCF7, MDA-MB-231, MDA-MB-468 cells, respectively. |
Western Blot Analysis[1]
| Cell Line: | BT-474, MCF7, MDA-MB-231, MDA-MB-468 cells |
| Concentration: | 0, 10, 20, 40 µM |
| Incubation Time: | 24 h |
| Result: | Decreased the expression of FoxM1 protein in a dose-dependent manner, and decreased teh expression of A-Raf, B-Raf, and C-Raf. |
Sepin-1 (10 mg/kg；静脉注射；每天一次，每周 5 天，持续 3 周) 在小鼠体内显示出抗肿瘤活性[2]。
| Animal Model: | SCID beige mice (MCF7 xenografts)[2] |
| Dosage: | 10 mg/kg |
| Administration: | I.v.; daily for 5 days a week for 3 weeks |
| Result: | Inhibited tumor growth. |
[1]. Zhang N, et al. Separase Inhibitor Sepin-1 Inhibits Foxm1 Expression and Breast Cancer Cell Growth. J Cancer Sci Ther. 2018;10(3):517.
[2]. Zhang N, et al. Identification and Characterization of Separase Inhibitors (Sepins) for Cancer Therapy. J Biomol Screen. 2014 Jul;19(6):878-89.