IC50: 0.56 ± 0.043 μM (HIF-1α), 8.46 ± 1.08 μM (DLL4)[1]
Steppogenin is a potent inhibitor of HIF-1α and DLL4, with IC50 values of 0.56 and 8.46 μM, respectively. Steppogenin can be sued for the research of angiogenic diseases, such as those involving solid tumors[1].
Steppogenin (0-10 μM, 24 h) 以剂量依赖性方式抑制 HEK293T 细胞缺氧条件下 HIF-1α 的转录活性和血管内皮细胞 (ECs) 中 VEGF 诱导的 DLL4 表达[1]。
Steppogenin (0-3 μM，6 h) 在缺氧条件下抑制 HIF-1α 靶基因（VEGF、GLUT1、CXCR4 和 CA9）的 mRNA 表达[1]。
Steppogenin (0-3 μM，16 h) 抑制 HIF-1α 蛋白水平，并抑制 VEGF、CXCR4 和 CA9 的蛋白水平[1]。
Steppogenin (0-3 μM，24 h) 抑制缺氧诱导的血管 EC 增殖和迁移以及 VEGF 诱导的 EC 球体发芽[1]。
RT-PCR[1]
| Cell Line: | A549 cells |
| Concentration: | 0, 0.3, 1, 3 μM |
| Incubation Time: | 6 h |
| Result: | Suppressed the mRNA expression of HIF-1α target genes (VEGF, GLUT1, CXCR4, and CA9) under poxic conditions. |
Western Blot Analysis[1]
| Cell Line: | HEK293T, A549, ARPE19 cells |
| Concentration: | 0, 0.3, 1, 3 μM |
| Incubation Time: | 16 h |
| Result: | Significantly suppressed HIF-1α protein levels in a dose-dependent manner. reduced nuclear expression of HIF-1α under poxic conditions. Inhibited protein levels of VEGF, CXCR4, and CA9 compared with the levels detected in the vehicle control group. Suppresseed VEGF-induced DLL4 protein expression. |
Steppogenin (2 mg/kg，腹腔注射，一次) 抑制肿瘤生长和血管生成[1]。
Steppogenin (2 mg/kg，腹腔注射，一次) 在肝脏和脾脏中的分布最高 (分别为 25.5 倍和 9.74 倍 AUC 比率)，T1/2 显著更高[1]。
Pharmacokinetic Parameters of Steppogenin in male C57BL/6 J mice[1].
| Cmax (ng/mL) | Tmax (h) | T1/2 (h) | AUC8h (ng/mL∗h) | AUC∞ (ng/mL∗h) | AUC ratio | |
| Plasma | 448 ± 113 | 0.25 | 0.49 ± 0.14 | 283 ± 98.9 | 284 ± 97.8 | 1 |
| Tumor | 635 ± 114 | 0.3 ± 0.1 | 1.87 ± 0.87 | 1078 ± 494 | 1252 ± 547 | 4.58 |
| Liver | 4319 ± 1063 | 0.25 | 1.72 ± 0.26 | 6733 ± 1300 | 6967 ± 1200 | 25.5 |
| Lung | 521 ± 181 | 0.25 | 0.36 ± 0.12 | 261 ± 96.1 | 280 ± 106 | 1.02 |
| Heart | 285 ± 15.2 | 0.25 | 0.2 | 107 ± 44.3 | 176.9 | 0.65 |
| Kidney | 1225 ± 463 | 0.25 | 0.33 ± 0.01 | 628 ± 234 | 624.7 ± 238 | 2.35 |
| Spleen | 6110 ± 2954 | 0.25 | 0.47 ± 0.01 | 2443 ± 1155 | 2663 ± 1289 | 9.74 |
| Brain | 309 ± 95.7 | 0.25 | 1.36 ± 0.46 | 191 ± 67 | 241 ± 75.4 | 0.88 |
| Animal Model: | C57BL/6 J mice (6-week-old, male, Lewis lung carcinoma (LLC) allograft tumor model)[1] |
| Dosage: | 2 mg/kg |
| Administration: | IP, once |
| Result: | Significantly suppressed tumor growth. |
| Animal Model: | C57BL/6 J mice (6-week-old, male, Lewis lung carcinoma (LLC) allograft tumor model)[1] |
| Dosage: | 2 mg/kg |
| Administration: | IP, once (Pharmacokinetic Analysis) |
| Result: | Showed the highest distribution to the liver and spleen (25.5-fold and 9.74-fold AUC ratio, respectively) with significantly higher T1/2. may not be accumulated even in the highly distributed tissues after the repeated administration of steppogenin. |
[1]. Cha S, et al. Steppogenin suppresses tumor growth and sprouting angiogenesis through inhibition of HIF-1α in tumors and DLL4 activity in the endothelium. Ptomedicine. 2023 Jan;108:154513.