WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H526646
CAS#: 869853-70-3
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.
Hodoodo Cat#: H526646
Name: VAS3947
CAS#: 869853-70-3
Chemical Formula: C14H10N6OS
Exact Mass: 310.06
Molecular Weight: 310.335
Elemental Analysis: C, 54.18; H, 3.25; N, 27.08; O, 5.16; S, 10.33
Synonym: VA-S3947; VA S3947; VAS3947
IUPAC/Chemical Name: 3-Benzyl-7-(2-oxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine
InChi Key: JVZDLDFNSCFLPM-UHFFFAOYSA-N
InChi Code: 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
SMILES Code: C12=NC=NC(SC3=NC=CO3)=C1N=NN2CC4=CC=CC=C4
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: 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.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| 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. |
| 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 |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 100.0 | 322.24 |
The following data is based on the product molecular weight 310.34 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. El Dor M, Dakik H, Polomski M, Haudebourg E, Brachet M, Gouilleux F, Prié G, Zibara K, Mazurier F. VAS3947 Induces UPR-Mediated Apoptosis through Cysteine Thiol Alkylation in AML Cell Lines. Int J Mol Sci. 2020 Jul 31;21(15):5470. doi: 10.3390/ijms21155470. PMID: 32751795; PMCID: PMC7432790. 2. Wind S, Beuerlein K, Eucker T, Müller H, Scheurer P, Armitage ME, Ho H, Schmidt HH, Wingler K. Comparative pharmacology of chemically distinct NADPH oxidase inhibitors. Br J Pharmacol. 2010 Oct;161(4):885-98. doi: 10.1111/j.1476-5381.2010.00920.x. PMID: 20860666; PMCID: PMC2970907. |
| In vitro protocol: | 1. El Dor M, Dakik H, Polomski M, Haudebourg E, Brachet M, Gouilleux F, Prié G, Zibara K, Mazurier F. VAS3947 Induces UPR-Mediated Apoptosis through Cysteine Thiol Alkylation in AML Cell Lines. Int J Mol Sci. 2020 Jul 31;21(15):5470. doi: 10.3390/ijms21155470. PMID: 32751795; PMCID: PMC7432790. 2. Wind S, Beuerlein K, Eucker T, Müller H, Scheurer P, Armitage ME, Ho H, Schmidt HH, Wingler K. Comparative pharmacology of chemically distinct NADPH oxidase inhibitors. Br J Pharmacol. 2010 Oct;161(4):885-98. doi: 10.1111/j.1476-5381.2010.00920.x. PMID: 20860666; PMCID: PMC2970907. |
| In vivo protocol: | TBD |
1: Caillot M, Zylbersztejn F, Maitre E, Bourgeais J, Hérault O, Sola B. ROS Overproduction Sensitises Myeloma Cells to Bortezomib-Induced Apoptosis and Alleviates Tumour Microenvironment-Mediated Cell Resistance. Cells. 2020 Oct 26;9(11):2357. doi: 10.3390/cells9112357. PMID: 33114738; PMCID: PMC7693395.
2: El Dor M, Dakik H, Polomski M, Haudebourg E, Brachet M, Gouilleux F, Prié G, Zibara K, Mazurier F. VAS3947 Induces UPR-Mediated Apoptosis through Cysteine Thiol Alkylation in AML Cell Lines. Int J Mol Sci. 2020 Jul 31;21(15):5470. doi: 10.3390/ijms21155470. PMID: 32751795; PMCID: PMC7432790.
3: Reis J, Massari M, Marchese S, Ceccon M, Aalbers FS, Corana F, Valente S, Mai A, Magnani F, Mattevi A. A closer look into NADPH oxidase inhibitors: Validation and insight into their mechanism of action. Redox Biol. 2020 May;32:101466. doi: 10.1016/j.redox.2020.101466. Epub 2020 Feb 15. PMID: 32105983; PMCID: PMC7042484.
4: Lu WJ, Li JY, Chen RJ, Huang LT, Lee TY, Lin KH. VAS2870 and VAS3947 attenuate platelet activation and thrombus formation via a NOX-independent pathway downstream of PKC. Sci Rep. 2019 Dec 11;9(1):18852. doi: 10.1038/s41598-019-55189-5. PMID: 31827142; PMCID: PMC6906488.
5: Kakoki M, Bahnson EM, Hagaman JR, Siletzky RM, Grant R, Kayashima Y, Li F, Lee EY, Sun MT, Taylor JM, Rice JC, Almeida MF, Bahr BA, Jennette JC, Smithies O, Maeda-Smithies N. Engulfment and cell motility protein 1 potentiates diabetic cardiomyopathy via Rac-dependent and Rac-independent ROS production. JCI Insight. 2019 Jun 20;4(12):e127660. doi: 10.1172/jci.insight.127660. PMID: 31217360; PMCID: PMC6629098.
6: Hecht N, Terveer N, Schollmayer C, Holzgrabe U, Meinel L. Opening NADPH oxidase inhibitors for in vivo translation. Eur J Pharm Biopharm. 2017 Jun;115:206-217. doi: 10.1016/j.ejpb.2017.03.001. Epub 2017 Mar 8. PMID: 28284727.
7: Schramm A, Matusik P, Osmenda G, Guzik TJ. Targeting NADPH oxidases in vascular pharmacology. Vascul Pharmacol. 2012 May-Jun;56(5-6):216-31. doi: 10.1016/j.vph.2012.02.012. Epub 2012 Mar 3. PMID: 22405985; PMCID: PMC3378316.
8: Wind S, Beuerlein K, Eucker T, Müller H, Scheurer P, Armitage ME, Ho H, Schmidt HH, Wingler K. Comparative pharmacology of chemically distinct NADPH oxidase inhibitors. Br J Pharmacol. 2010 Oct;161(4):885-98. doi: 10.1111/j.1476-5381.2010.00920.x. PMID: 20860666; PMCID: PMC2970907.
