In Vitro: SB-435495 hydrochloride inhibits CYP450 3A4 with an IC50 of 10 μM and the black membrane permeability is 0.017 cm/h. SB-435495 (5 μM; 24 h) hydrochloride significantly inhibits the expression of Lp-PLA2 protein, while increases the expression levels of AMPKα and phosphorylated-AMPKα (T172) in oxLDL-exposed HUVECs. SB-435495 (5 μM; 24-72 h) hydrochloride significantly increases cell viability and NO expression, significantly decreases ET-1 expression in the oxLDL-exposed HUVECs.
In Vivo: SB-435495 (10 mg/kg; p.o.; once) hydrochloride inhibits plasma Lp-PLA2 in the WHHL rabbit. SB-435495 (10 mg/kg; i.p.; daily for 28 days) hydrochloride effectively suppresses blood–retinal barrier (BRB) breakdown in Streptozotocin (HY-13753)-diabetic Brown Norway rats.