| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Vacuolin-1 targets lysosomal exocytosis and PIKfyve. It blocks the Ca2+-dependent exocytosis of lysosomes, preventing the release of lysosomal content. It is also a potent and selective inhibitor of PIKfyve, a lipid kinase involved in endosomal trafficking. By inhibiting PIKfyve, it impairs lysosomal maturation and inhibits late autophagy.
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| ln Vitro |
Ionomycin-induced lysosomal exocytosis is inhibited by vacuolin-1 (1 μM; 1 h pretreatment), but amplified exocytosis is unaffected. It totally suppresses Lamp-1's surface expression and induces lysosomal vacuolation (A) [1]. The inner and limiting membrane properties of endosomes and lysosomes are disrupted by vacuolin-1 (1 μM; 20-180 min). Vacuolin-1 enhances the union of the inner membrane and the limiting membrane, according to ultrastructural studies [1]. β-hexosaminidase release from lysosomes that is reliant on Ca2+ is inhibited by vacuolin-1 (5 or 10 μM; 2 hours). Ionomycin is predicted to release 18–20% of lysosomal β-hexosaminidase in HeLa cells. In contrast to cells not exposed to ionomycin (4%) no more β-hexosaminidase was produced when cells were pretreated with vacuolin-1 [1].
In vitro, vacuolin-1 blocks the Ca2+-dependent exocytosis of lysosomes and prevents the release of lysosomal content without affecting the process of resealing. It inhibits autophagy by impairing lysosomal maturation and potently and reversibly inhibits autophagosome-lysosome fusion by activating RAB5A. It is a potent and selective PIKfyve inhibitor. |
| ln Vivo |
Specific in vivo data for vacuolin-1 are not detailed in the available literature. However, as a potent inhibitor of lysosomal exocytosis and PIKfyve, it could be used in preclinical studies to investigate the role of these processes in various diseases, including cancer and neurodegeneration.
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| Enzyme Assay |
The activity of vacuolin-1 can be assessed using cell-free assays to measure its inhibition of PIKfyve. The lipid kinase is incubated with its substrate, phosphatidylinositol, and ATP in the presence of varying concentrations of the inhibitor. The production of phosphatidylinositol 3,5-bisphosphate is measured. The IC50 for PIKfyve inhibition is determined from dose-response curves.
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| Cell Assay |
To evaluate the cellular effects of vacuolin-1, cells are treated with the compound, and lysosomal exocytosis is assessed by measuring the release of lysosomal enzymes or by using fluorescent reporters. Autophagy is assessed by measuring LC3-II accumulation or p62 degradation. The effects on endosomal trafficking and lysosomal morphology are evaluated by microscopy.
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| Animal Protocol |
In vivo studies with vacuolin-1 would typically involve administration to animals via oral or parenteral routes. Models of cancer, neurodegeneration, or other diseases involving lysosomal dysfunction could be used to evaluate the compound's effects.
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| ADME/Pharmacokinetics |
Vacuolin-1 has a molecular formula of C22H24IN7O and a molecular weight of approximately 500 (exact value not specified in the available literature). Its CAS number is 351986-85-1. The compound is a cell-permeable lysosomal exocytosis inhibitor. It is soluble in DMSO and other organic solvents. The purity is typically >98%.
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| Toxicity/Toxicokinetics |
Specific toxicology data for vacuolin-1 are not detailed in the available literature. However, as an inhibitor of lysosomal function, it may have significant cellular effects. As with all research compounds, standard safety precautions should be taken during handling.
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| References |
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| Additional Infomation |
Vacuolin-1 is a potent and cell-permeable lysosomal exocytosis inhibitor used as a research tool to study lysosomal function and autophagy. It is also a potent and selective PIKfyve inhibitor. It is a valuable tool for studying the roles of lysosomes and PIKfyve in various cellular processes and diseases. It is not a clinically approved drug.
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| Molecular Formula |
C26H24N7OI
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| Molecular Weight |
577.41906
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| Exact Mass |
577.108
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| CAS # |
351986-85-1
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| PubChem CID |
9661141
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
719.7±70.0 °C at 760 mmHg
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| Flash Point |
389.1±35.7 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.706
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| LogP |
4.41
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
634
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1COCCN1C2=NC(=NC(=N2)N/N=C/C3=CC(=CC=C3)I)N(C4=CC=CC=C4)C5=CC=CC=C5
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| InChi Key |
JMEJTSRAQUFNOP-TURZUDJPSA-N
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| InChi Code |
InChI=1S/C26H24IN7O/c27-21-9-7-8-20(18-21)19-28-32-24-29-25(33-14-16-35-17-15-33)31-26(30-24)34(22-10-3-1-4-11-22)23-12-5-2-6-13-23/h1-13,18-19H,14-17H2,(H,29,30,31,32)/b28-19+
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| Chemical Name |
2-N-[(E)-(3-iodophenyl)methylideneamino]-6-morpholin-4-yl-4-N,4-N-diphenyl-1,3,5-triazine-2,4-diamine
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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) |
DMSO : ~10 mg/mL (~17.32 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 1 mg/mL (1.73 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1 mg/mL (1.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7318 mL | 8.6592 mL | 17.3184 mL | |
| 5 mM | 0.3464 mL | 1.7318 mL | 3.4637 mL | |
| 10 mM | 0.1732 mL | 0.8659 mL | 1.7318 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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