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. 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 IC 50 of 12 µM. VAS3947 triggers cell proliferation arrest and death independently of anti-NOX activity. The IC 50 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. VAS3947 decreases ROS levels. VAS3947 triggers endoplasmic reticulum (ER) stress and consequent unfolding protein response (UPR). VAS3947 attenuates platelet activation and thrombus formation via a NOX-independent pathway downstream of PKC 3] . MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo NADPH 氧化酶抑制剂 MCE has not independently confirmed the accuracy of these methods. They are for reference only.

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