Steppogenin

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]. IC50 & Target:IC50: 0.56 ± 0.043 μM (HIF-1α), 8.46 ± 1.08 μM (DLL4)^[1] 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^[1].
Steppogenin (0-3 μM, 6 h) suppresses the mRNA expression of HIF-1α target genes (VEGF, GLUT1, CXCR4, and CA9) under hypoxic conditions^[1].
Steppogenin (0-3 μM, 16 h) suppresses HIF-1α protein levels, and inhibits protein levels of VEGF, CXCR4, and CA9^[1].
Steppogenin (0-3 μM, 24 h) suppresses hypoxia-induced vascular EC proliferation and migration as well as VEGF-induced sprouting of EC spheroids^[1].
In Vivo:Steppogenin (2 mg/kg, IP, once) inhibits tumor growth and angiogenesis^[1].
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^[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