| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
SKI V targets sphingosine kinase (SPHK), specifically SPHK1, which is a key enzyme in the sphingolipid pathway that catalyzes the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P). S1P is a potent signaling molecule involved in cell proliferation, survival, and migration. SKI V also inhibits PI3K (IC50 = 6 μM), a key enzyme in the PI3K/AKT/mTOR signaling pathway that regulates cell growth and survival.
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| ln Vitro |
SKI V does not inhibit PKC-α and has weak activity against ERK2 (IC50 for hERK2 is 80 μM)[1]. SKI V (10 μM; for 24 hours) causes apoptosis and suppresses the growth of cancer cells [1]. SKI V decreased the levels of phospho-Akt and phospho-MEK (0.2, 1, 5 μM; 1 hour pretreatment). After 16 hours of serum starvation, near-confluent JC cell cultures received a 1-hour SKI V pretreatment [2]. SKI V suppresses the growth of tumor cells and sphingosine kinase (SK) at an IC50 of approximately 2 μM [1]. In MDA-MB-231 cells, SKI V (20 μg/ml) suppresses both endogenous and purified SK [1]. In JC cells, SKI V (0.2, 1, 5 μM) suppresses the production of intracellular S1P in a dose-dependent manner [2].
SKI V exhibits potent in vitro activity. It inhibits GST-hSK (sphingosine kinase) with an IC50 of 2 μM. It inhibits hPI3k with an IC50 of 6 μM. It has weak activity toward ERK2 (IC50 of 80 μM) and does not inhibit PKC-α. It induces apoptosis and has antitumor activity in cellular studies. |
| ln Vivo |
In comparison with control rats, SKI V (75 mg/kg; i.p.; days 1, 5, 9, 15) significantly slowed tumor growth (reduction of >50% on day 18) [1].
In vivo, SKI V induces apoptosis and displays antitumor activity. Its ability to reduce S1P formation and inhibit PI3K contributes to its anticancer effects. Further in vivo studies are needed to fully characterize its efficacy and therapeutic potential. |
| Enzyme Assay |
Non-cellular assays for SKI V involve measuring its inhibition of sphingosine kinase (SPHK) and PI3K enzyme activities. These assays use recombinant enzymes and radiolabeled or fluorescent substrates. The enzyme is incubated with the substrate and varying concentrations of SKI V. The reduction in product formation is measured to determine the IC50.
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| Cell Assay |
Cell proliferation assay[1]
Cell Types: T24 tumor cell Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Inhibition of cancer cell proliferation. Apoptosis analysis[1] Cell Types: T24 tumor cells Tested Concentrations: 10 μM Incubation Duration: 24 hrs (hours) Experimental Results: Induction of apoptosis. Western Blot Analysis[2] Cell Types: JC Cell Tested Concentrations: 0.2, 1, 5 μM Incubation Duration: 1 hour pretreatment Experimental Results: diminished levels of phospho-Akt and phospho-MEK. In vitro cellular assays for SKI V are conducted in cancer cell lines. Cells are treated with the compound, and cell viability is measured using MTT or CellTiter-Glo assays. Apoptosis is assessed by Annexin V staining, caspase activity assays, or PARP cleavage. Sphingosine-1-phosphate (S1P) levels are measured by LC-MS to confirm target engagement. |
| Animal Protocol |
Animal/Disease Models: 6-8 weeks old BALB/c female mice, JC breast cancer cells [1]
Doses: 75 mg/kg Route of Administration: IP; results on days 1, 5, 9, and 15: compared with control animals Tumor growth was Dramatically diminished (>50% reduction on day 18) compared with tumor growth. In vivo animal experiments with SKI V are conducted in mouse xenograft models of cancer. Tumor-bearing mice are administered SKI V, and tumor growth is monitored. Tumor tissues are harvested for analysis of S1P levels, PI3K/AKT pathway activity, and apoptosis markers. |
| ADME/Pharmacokinetics |
SKI V has a molecular weight of 318.37 and is soluble in DMSO. It is typically stored as a powder at 2-8°C. Its pharmacokinetic properties, such as bioavailability and half-life, would need to be characterized for in vivo use.
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| Toxicity/Toxicokinetics |
SKI V is considered to have a manageable toxicity profile based on its use as a research compound. However, comprehensive toxicological data are not extensively published. The compound is intended for research use only and is not approved for human therapeutic use.
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| References | |
| Additional Infomation |
3',4'-Dihydroxyaurone is a hydroxyaurone, meaning that the aurone is substituted with hydroxyl groups at the 3' and 4' positions; it is the predominant form at pH 7.3. It exhibits inhibitory activity against multiple isoforms of the histone deacetylase complex (HDAC). It is an EC 3.5.1.98 (histone deacetylase) inhibitor. It is a hydroxyaurone belonging to the catechol group. Its function is related to 2',3,4-trihydroxytrans-chalcone.
SKI V is a potent, noncompetitive inhibitor of sphingosine kinase (SPHK) (IC50 = 2 μM) and PI3K (IC50 = 6 μM). It reduces S1P formation, induces apoptosis, and has antitumor activity. It is used in cancer research to study sphingolipid and PI3K signaling pathways. |
| Molecular Formula |
C15H10O4
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|---|---|
| Molecular Weight |
254.2375
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| Exact Mass |
254.057
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| CAS # |
24418-86-8
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| PubChem CID |
5793932
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.9
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
19
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| Complexity |
390
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C(=C([H])C2C([H])=C([H])C(=C(C=2[H])O[H])O[H])C(C2=C([H])C([H])=C([H])C([H])=C12)=O
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| InChi Key |
HCBULGQMULJTCM-ZSOIEALJSA-N
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| InChi Code |
InChI=1S/C15H10O4/c16-11-6-5-9(7-12(11)17)8-14-15(18)10-3-1-2-4-13(10)19-14/h1-8,16-17H/b14-8-
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| Chemical Name |
(2Z)-2-[(3,4-dihydroxyphenyl)methylidene]-1-benzofuran-3-one
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| Synonyms |
SKI V; SKI-V
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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 |
| 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 : ~50 mg/mL (~196.66 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.83 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL 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: 2.5 mg/mL (9.83 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline 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 | 3.9333 mL | 19.6665 mL | 39.3329 mL | |
| 5 mM | 0.7867 mL | 3.9333 mL | 7.8666 mL | |
| 10 mM | 0.3933 mL | 1.9666 mL | 3.9333 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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