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Steppogenin

(Synonyms: 草大戟素) 目录号 : GC69956

Steppogenin 是一种有效的 HIF-1α 和 DLL4 的抑制剂,其 IC50 值分别为 0.56 和 8.46 μM。Steppogenin 可用于血管生成疾病的研究,如实体瘤。

Steppogenin Chemical Structure

Cas No.:56486-94-3

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5mg
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产品描述

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
Plasma448 ± 1130.250.49 ± 0.14283 ± 98.9284 ± 97.81
Tumor635 ± 1140.3 ± 0.11.87 ± 0.871078 ± 4941252 ± 5474.58
Liver4319 ± 10630.251.72 ± 0.266733 ± 13006967 ± 120025.5
Lung521 ± 1810.250.36 ± 0.12261 ± 96.1280 ± 1061.02
Heart285 ± 15.20.250.2107 ± 44.3176.90.65
Kidney1225 ± 4630.250.33 ± 0.01628 ± 234624.7 ± 2382.35
Spleen6110 ± 29540.250.47 ± 0.012443 ± 11552663 ± 12899.74
Brain309 ± 95.70.251.36 ± 0.46191 ± 67241 ± 75.40.88

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.

Chemical Properties

Cas No. 56486-94-3 SDF Download SDF
别名 草大戟素
分子式 C15H12O6 分子量 288.25
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