VAS 3947

VAS 3947, a specific NADPH oxidase (NOX) inhibitor, exerts a potent antiplatelet effect. VAS3947 induces apoptosis independently of anti-NOX activity, via UPR activation, mainly due to aggregation and misfolding of proteins^[1][2]. In Vitro: VAS3947 consistently inhibits NADPH oxidase activity in low micromolar concentrations, and interferes neither with ROS detection nor with XOD or eNOS activities. VAS3947 (30 µM) does not interfere with xanthine/XOD-derived L012 signals, suggesting this compound is free of antioxidant or scavenging effects relevant to ROS detection. In CaCo-2 cell homogenates, VAS3947 completely blocks NADPH-dependent ROS production with an IC₅₀ of 12 µM^[1].
VAS3947 triggers cell proliferation arrest and death independently of anti-NOX activity. The IC₅₀ values of the different cell lines ranges from 2.6 ± 0.6 µM for the most sensitive cell line MV-4-11 to 4.9 µM for THP-1, the least sensitive^[2].
VAS3947 decreases ROS levels. VAS3947 triggers endoplasmic reticulum (ER) stress and consequent unfolding protein response (UPR)^[2].
VAS3947 attenuates platelet activation and thrombus formation via a NOX-independent pathway downstream of PKC^3]. In Vivo: NADPH 氧化酶抑制剂