SB-435495 is a potent, selective, reversible, non-covalent and orally active Lp-PLA2 inhibitor with an IC50 of 0.06 nM[1][3].
SB-435495 抑制 CYP450 3A4 的 IC50 为 10 μM，膜通透性为 0.017 cm/h[1]。
SB-435495 (5 μM; 24 h) 显著抑制 Lp-PLA2 蛋白的表达，同时提高 oxLDL 暴露 HUVECs 中 AMPKα 和磷酸化-AMPKα (T172) 的表达水平[2]。
SB-435495 (5 μM; 24-72 h) 在 oxLDL 暴露 HUVECs 中显著增加细胞活力和 NO 表达，显著降低 ET-1 表达[2]。
Western Blot Analysis[2]
| Cell Line: | oxLDL-exposed human umbilical vein endothelial cells |
| Concentration: | 5 μM |
| Incubation Time: | 24 h |
| Result: | The expression of Lp-PLA2 protein was significantly inhibited. Increased the expression levels of AMPKα and phosphorylated-AMPKα (T172). |
Cell Viability Assay[2]
| Cell Line: | oxLDL-exposed human umbilical vein endothelial cells |
| Concentration: | 5 μM |
| Incubation Time: | 24, 48 and 72 h |
| Result: | Significantly increased cell viability. |
SB-435495 (10 mg/kg; p.o.; once) 抑制 WHHL 兔血浆 Lp-PLA2 [1]。
SB-435495 (10 mg/kg; i.p.; daily for 28 days) 在 Streptozotocin 糖尿病褐挪威大鼠中有效抑制血视网膜屏障 (BRB) 的破坏[3]。
[1]. Blackie JA, et al. The discovery of SB-435495. A potent, orally active inhibitor of lipoprotein-associated phospholipase A(2) for evaluation in man. Bioorg Med Chem Lett. 2002 Sep 16;12(18):2603-6.
[2]. Yang L, et al. AMP-activated protein kinase mediates the effects of lipoprotein-associated phospholipase A2 on endothelial dysfunction in atherosclerosis. Exp Ther Med. 2017 Apr;13(4):1622-1629.
[3]. Canning P, et al. Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7213-8.