| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
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| Other Sizes |
Purity: ≥98%
| Targets |
MKK4 (activator)
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| ln Vitro |
Vacquinol-1 induces rapid and specific cell death of glioma cells with IC50 of 3.14 μM via membrane ruffling, cell rounding, massive macropinocytic vacuole accumulation, ATP depletion, and cytoplasmic membrane rupture.
Kinase Assay: Vacquinol-1 (also known as NSC-13316; NSC13316) is an MKK4 (mitogen-activated protein kinase kinase 4) activator with antitumor activity. Cell Assay: Cell viability is measured using CellTiter-Glo Luminescent Cell Viability Assay according to the manufacturer’s instructions. Vacquinol-1 functions as a specific activator of mitogen-activated protein kinase kinase 4 (MKK4), also known as MAP2K4 or MEK4. In glioblastoma cells, it triggers a non-apoptotic cell death pathway characterized by catastrophic vacuolization driven by massive macropinocytosis, leading to ATP depletion and cytoplasmic membrane rupture. The compound induces rapid and specific cell death of glioma cells with an IC50 of 3.14 µM via membrane ruffling, cell rounding, massive macropinocytic vacuole accumulation, ATP depletion, and cytoplasmic membrane rupture. It displays high cytotoxicity against glioma cells, resulting in complete loss of viability as measured by ATP depletion. The compound shows no effect on caspase activity at any concentration or time point, unlike staurosporine. It selectively targets glioma cells in mixed cocultures with human fibroblasts. |
| ln Vivo |
The ability of vacquinol-1 to attenuate tumor progression was previously tested in a mouse model for human GBM. Vacquinol-1 or vehicle (DMSO) were intracranially administered into the site of original cell deposit 6 weeks after engraftment. Results showed that tumors were invariantly smaller, and the area of necrosis and hGFAP and hNestin immunoreactivity was significantly reduced. Moreove, only tumor cells in vacquinol-1-treated mice showed a massive LAMP1 staining.
Vacquinol-1 induces rapid and specific cell death of glioma cells with an IC50 of 3.14 µM via membrane ruffling, cell rounding, massive macropinocytic vacuole accumulation, ATP depletion, and cytoplasmic membrane rupture. It displays high cytotoxicity against glioma cells, resulting in complete loss of viability as measured by ATP depletion. The compound shows no effect on caspase activity at any concentration or time point, unlike staurosporine. It selectively targets glioma cells in mixed cocultures with human fibroblasts. In mice bearing U3013 MG tumors, Vacquinol-1 (15 µM intracranial injection or 20 mg/kg oral administration) attenuates tumor growth and prolongs survival. The compound displays excellent in vivo pharmacokinetics and brain exposure, attenuates disease progression in a glioblastoma animal model. It has high oral bioavailability and good brain penetration. |
| Enzyme Assay |
MKK4 activation is assessed by measuring phosphorylation of MKK4 and its downstream targets JNK. Glioma cells are treated with Vacquinol-1 at 7.5 µM, and MKK4 phosphorylation is analyzed by Western blot. Kinase assays may also be performed using recombinant MKK4 and appropriate substrates to confirm direct activation. The compound's ability to activate the MAPK pathway is confirmed through these assays.
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| Cell Assay |
Cell viability is measured using CellTiter-Glo Luminescent Cell Viability Assay in glioma cell lines treated with Vacquinol-1 at various concentrations. ATP depletion is measured using luminescent ATP detection assays. Vacuolization is assessed by light microscopy and fluorescence staining. Caspase activity is measured using fluorogenic substrates to confirm non-apoptotic cell death mechanism. The compound's selective cytotoxicity against GBM cells while sparing normal cells is confirmed in mixed coculture assays.
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| Animal Protocol |
Dissolved in DMSO; 15 μM or 20 mg/kg; Intracranial injection, i.p., p.o.
Mice bearing U3013MG tumors In mice bearing U3013 MG tumors, Vacquinol-1 is administered via intracranial injection (15 µM) or oral gavage (20 mg/kg). Tumor growth is monitored, and survival is recorded. In the mouse model for human GBM, Vacquinol-1 or vehicle (DMSO) is intracranially administered into the site of original cell deposit 6 weeks after engraftment. The compound demonstrates efficacy in attenuating disease progression and prolonging survival in a glioblastoma multiforme (GBM) mouse model. |
| ADME/Pharmacokinetics |
Vacquinol-1 demonstrates excellent in vivo pharmacokinetics with a plasma half-life of 52 hours. It has high oral bioavailability and good brain penetration. The compound is stable in vivo with favorable PK properties. Different stereoisomers of Vacquinol-1 display stereospecific pharmacokinetic and pharmacodynamic features. Procurement with defined stereochemistry is critical to ensure reproducible results. The compound is soluble in DMSO but not in water.
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| Toxicity/Toxicokinetics |
Comprehensive toxicology data for Vacquinol-1 are limited. Preclinical studies indicate that the compound has little effect on normal cells such as fibroblasts and embryonic stem cells, suggesting a favorable selectivity profile. Standard laboratory safety precautions should be observed during handling. The compound has not been evaluated in formal toxicology studies for human use. The compound has not entered clinical trials.
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| References |
Cell.2014 Apr 10;157(2):313-28.
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| Additional Infomation |
Vacquinol-1 was identified as a small molecule that induces massive vacuolization of glioblastoma cells through a non-apoptotic cell death pathway. It disrupts autophagy and macropinocytosis in tumor cells, leading to catastrophic failure of the endolysosomal system. The compound represents a potential therapeutic for glioblastoma multiforme and has been investigated in preclinical models for its oncolytic efficacy. Its exquisite SAR—where minor modifications to the β-hydroxypiperidine or quinoline scaffold ablate potency—makes it an irreplaceable positive control for GBM phenotypic screening and in vivo efficacy benchmarking. Vacquinol-1 has not entered clinical trials and remains a research tool for studying glioblastoma biology and non-apoptotic cell death pathways.
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| Molecular Formula |
C21H23CL3N2O
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|---|---|---|
| Molecular Weight |
425.779122591019
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| Exact Mass |
424.088
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| CAS # |
2309312-85-2
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| Related CAS # |
Vacquinol-1 dihydrochloride;2309312-85-2
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| PubChem CID |
129896712
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
426
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=CC(=CC=1)C1=CC(=C2C=CC=CC2=N1)C(C1CCCCN1)O.Cl.Cl
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 10 mg/mL (23.49 mM) in 50% PEG300 +50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3486 mL | 11.7432 mL | 23.4863 mL | |
| 5 mM | 0.4697 mL | 2.3486 mL | 4.6973 mL | |
| 10 mM | 0.2349 mL | 1.1743 mL | 2.3486 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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