Steppogenin is a potent inhibitor of HIF-1α and DLL4 , with IC 50 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
In Vitro
Steppogenin (0-10 μM, 24 h) inhibit the transcriptional activity of HIF-1α under hypoxic conditions in HEK293T cells and VEGF-induced DLL4 expression in vascular endothelial cells (ECs) in a dose-dependent manner. Steppogenin (0-3 μM, 6 h) suppresses the mRNA expression of HIF-1α target genes (VEGF, GLUT1, CXCR4, and CA9) under hypoxic conditions. Steppogenin (0-3 μM, 16 h) suppresses HIF-1α protein levels, and inhibits protein levels of VEGF, CXCR4, and CA9. Steppogenin (0-3 μM, 24 h) suppresses hypoxia-induced vascular EC proliferation and migration as well as VEGF-induced sprouting of EC spheroids. MCE has not independently confirmed the accuracy of these methods. They are for reference only. RT-PCRCell 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 hypoxic conditions. Western Blot AnalysisCell 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 hypoxic 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.
In Vivo
Steppogenin (2 mg/kg, IP, once) inhibits tumor growth and angiogenesis . Steppogenin (2 mg/kg, IP, once) shows the highest distribution to the liver and spleen (25.5-fold and 9.74-fold AUC ratio, respectively) with significantly higher T 1/2 . Pharmacokinetic Parameters of Steppogenin in male C57BL/6 J mice . C max (ng/mL) T max (h) T 1/2 (h) AUC 8h (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 MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: C57BL/6 J mice (6-week-old, male, Lewis lung carcinoma (LLC) allograft tumor model) 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) 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 T 1/2 . may not be accumulated even in the highly distributed tissues after the repeated administration of steppogenin.
IC50& Target:IC50: 0.56 ± 0.043 μM (HIF-1α), 8.46 ± 1.08 μM (DLL4)
