VAS3947

• CAS: 869853-70-3
• Catalog Number: ACM869853703
• Category: Inhibitors
• Molecular Weight: 310.34
• Molecular Formula: C14H10N6OS
• Description: VAS3947 is a selective inhibitor of NADPH oxidase activity in low micromolar concentrations, interfering neither with ROS detection nor with XOD or eNOS activities. VAS3947 induces apoptosis in AML cells independently of its anti-NOX activity. VAS3947 thiol alkylates cysteine residues of glutathione (GSH), while also interacting with proteins. Remarkably, VAS3947 decreased detectable GSH in the MV-4-11 cell line, thereby suggesting possible oxidative stress induction. Overall, VAS3947 induces apoptosis independently of anti-NOX activity, via UPR activation, mainly due to aggregation and misfolding of proteins.
• Synonyms: VA-S3947; VA S3947; VAS3947
• IUPAC Name: 3-Benzyl-7-(2-oxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine
• Canonical SMILES: C12=NC=NC(SC3=NC=CO3)=C1N=NN2CC4=CC=CC=C4
• InChI: InChI=1S/C14H10N6OS/c1-2-4-10(5-3-1)8-20-12-11(18-19-20)13(17-9-16-12)22-14-15-6-7-21-14/h1-7,9H,8H2
• InChI Key: JVZDLDFNSCFLPM-UHFFFAOYSA-N
• Solubility: Soluble in DMSO
• Appearance: Solid powder
• Shelf Life: >2 years if stored properly
• Storage: Dry, dark and at 0-4 °C for short term (days to weeks) or -20 °C for long term (months to years).
• Biological Target: VAS 3947, a specific NADPH oxidase (NOX) inhibitor, exerts a potent antiplatelet effect that induces apoptosis independently of anti-NOX activity, via UPR activation, mainly due to aggregation and misfolding of proteins.
• Drug Formulation: This drug may be formulated in DMSO
• Elemental Analysis: C, 54.18; H, 3.25; N, 27.08; O, 5.16; S, 10.33
• Exact Mass: 310.0637
• HS Tariff Code: 2934.99.9001
• In Vitro Activity: To determine the cytotoxic effects of VAS3947, eight AML cell lines, covering M0 to M5 stages of the French-American-British (FAB) classification, were treated with increasing concentrations (0.5 µM to 20 µM) of this inhibitor for 72 h. An average dose of 4 µM VAS3947 was chosen for the following experiments. After only 1 day-exposure at this concentration, all cell lines showed reduced cell numbers compared to their corresponding controls, and the difference increased over time. The VAS3947-induced decrease in cell proliferation was mostly explained by apoptosis for KG-1a, KG-1, ML-2, and MV-4-11 cells. The absence of NOX activity in THP-1 and its induction by phorbol 12-myristate 13-acetate (PMA) was confirmed, which, however, is efficiently inhibited by VAS3947. Thus, VAS3947 reduces cell growth and induces cell death in the absence of NOX activity, thereby suggesting possible off-target effects.; Reference: Int J Mol Sci. 2020 Jul 31;21(15):5470. https://pubmed.ncbi.nlm.nih.gov/32751795/; To determine the cytotoxic effects of VAS3947, eight AML cell lines, covering M0 to M5 stages of the French-American-British (FAB) classification, were treated with increasing concentrations (0.5 µM to 20 µM) of this inhibitor for 72 h. An average dose of 4 µM VAS3947 was chosen for the following experiments. After only 1 day-exposure at this concentration, all cell lines showed reduced cell numbers compared to their corresponding controls, and the difference increased over time. The VAS3947-induced decrease in cell proliferation was mostly explained by apoptosis for KG-1a, KG-1, ML-2, and MV-4-11 cells. The absence of NOX activity in THP-1 and its induction by phorbol 12-myristate 13-acetate (PMA) was confirmed, which, however, is efficiently inhibited by VAS3947. Thus, VAS3947 reduces cell growth and induces cell death in the absence of NOX activity, thereby suggesting possible off-target effects.; Reference: Int J Mol Sci. 2020 Jul 31;21(15):5470. https://pubmed.ncbi.nlm.nih.gov/32751795/
• In Vivo Activity: TBD
• Shipping: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
• Stock Solution Storage: 0-4 °C for short term (days to weeks), or -20 °C for long term (months).