SB-435495 hydrochloride

SB-435495 hydrochloride is a potent, selective, reversible, non-covalent and orally active Lp-PLA2 inhibitor with an IC50 of 0.06 nM[1][3].

Signaling Pathways >> Metabolic Enzyme/Protease >> Phospholipase

Research Areas >> Metabolic Disease

Lp-PLA2:0.06 nM (IC50)

SB-435495 hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride 抑制 WHHL 兔血浆 Lp-PLA2 [1]。 SB-435495 (10 mg/kg; i.p.; daily for 28 days) hydrochloride 在 Streptozotocin (HY-13753) 糖尿病褐挪威大鼠中有效抑制血视网膜屏障 (BRB) 的破坏[3]。 Animal Model: WHHL rabbit[1] Dosage: 10 mg/kg Administration: Oral, once Result: Inhibited plasma Lp-PLA2 in the WHHL rabbit.

[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.