Skp2 inhibitor 1 (compound 14i) is a potent and selective Skp2 inhibitor against the Skp2-Cks1 interaction with an IC50 of 2.8 μM. Skp inhibitor 1 exhibits anticancer activity[1].
Skp2 inhibitor 1 (2.8 μM，72 小时) 干扰 Skp2-Cks1 相互作用，对 PC-3 和 MGC-803 细胞的 IC50 值分别为 4.8 μM和 7.0 μM[1]。
Skp2 inhibitor 1 (10 μM，48 小时) 抑制 PC-3 和 MGC-803 细胞的增殖和迁移，诱导细胞在 S 期阻滞并促进细胞凋亡[1]。
Cell Viability Assay[1]
| Cell Line: | PC-3 , MGC-803 |
| Concentration: | 0-10 μM |
| Incubation Time: | 72 h |
| Result: | Against the Skp2-Cks1 interaction with an IC50 value of 2.8 μM, and against PC-3 and MGC-803 cells with IC50 values of 4.8 and 7.0 μM, respectively. |
Apoptosis Analysis[1]
| Cell Line: | PC-3 , MGC-803 |
| Concentration: | 2.5 μM , 5 μM , 10 μM |
| Incubation Time: | 0-48 h |
| Result: | Leaded to cell cycle S-phase arrest in a dose-dependent manner, and induced apoptosis in a dose-dependent manner, such as nuclear fragmentation, condensation, and cell shrinkage. |
Cell Proliferation Assay[1]
| Cell Line: | PC-3 , MGC-803 |
| Concentration: | 0.5 μM , 1 μM , 2 μM |
| Incubation Time: | 10 days |
| Result: | Inhibited colony-forming abilities in a dose-dependent manner. |
Cell Migration Assay [1]
| Cell Line: | PC-3 , MGC-803 |
| Concentration: | 2.5 μM , 5 μM , 10 μM |
| Incubation Time: | 48 h |
| Result: | Inhibited migration in a dose-dependent manner. |
Cell Invasion Assay[1]
| Cell Line: | PC-3 , MGC-803 |
| Concentration: | 0.5 μM , 1 μM , 2 μM |
| Incubation Time: | 48 h |
| Result: | Inhibited invasion in a dose-dependent manner. |
Western Blot Analysis[1]
| Cell Line: | PC-3 , MGC-803 |
| Concentration: | 2.5 μM , 5 μM , 10 μM |
| Incubation Time: | 0-48 h |
| Result: | Inhibited the protein levels of Skp2 in a dose-dependent manner, restored the expression of p21 and p27 in a time-dependent manner. |
Skp2 inhibitor 1 (10 mg/kg; 25 mg/kg, 50 mg/kg；腹腔注射/2天，21天) 在 NOD-SCID 小鼠异种移植模型中显著抑制肿瘤生长且没有明显毒性。此外，Skp2 inhibitor 1 (50mg/Kg/2天) 处理完全抑制肿瘤生长[1]。
Skp2 inhibitor 1通过抑制 Skp2 信号通路降低肿瘤恶性程度，并上调肿瘤组织中细胞凋亡的比例[1]。
| Animal Model: | The xenograft models of PC-3 and MGC-803 cells in NOD-SCID mice[1]. |
| Dosage: | 10 mg/kg; 25 mg/kg, 50 mg/kg |
| Administration: | Intraperitoneal injection (i.p.) |
| Result: | Inhibited tumor growth without obvious toxicity, the tumor growth inhibition ratio was 55.68, 71.86, and 90.42% with 10, 25, and 50 mg/Kg/2 day, respectively. |
[1]. Zhang K, et al. Discovery of Novel 1,3-Diphenylpyrazine Derivatives as Potent S-Phase Kinase-Associated Protein 2 (Skp2) Inhibitors for the Treatment of Cancer. J Med Chem. 2023 Jun 8;66(11):7221-7242.