| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| Other Sizes |
| Targets |
SKI-178 targets sphingosine kinase-1 (SphK1) and SphK2. These enzymes catalyze the phosphorylation of sphingosine to sphingosine-1-phosphate (S1P), a bioactive lipid that promotes cell survival and proliferation. By inhibiting SphK1 and SphK2, SKI-178 disrupts S1P signaling, leading to apoptosis. It induces prolonged mitosis followed by apoptotic cell death through the intrinsic apoptotic cascade. This mechanism underlies its potent activity against AML and other cancers.
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| ln Vitro |
Prolonged Bcl-2 phosphorylation is linked to liver cancer cell mortality mediated by SKI-178 (5 μM; 24 hours) [1].
In vitro, SKI-178 is a potent SphK1 and SphK2 inhibitor with IC50 values ranging from 0.1 to 1.8 µM in various AML cell lines. It is cytotoxic at IC50 concentrations ranging from 1.8 to 0.1 µM in both drug-sensitive and multi-drug resistant cancer cell lines. It induces prolonged mitosis followed by apoptotic cell death through the intrinsic apoptotic cascade. It is a valuable tool for studying the role of sphingosine kinases in cancer and for developing new therapies for AML. |
| ln Vivo |
In the MLL-AF9 model, SKI-178 (20 mg/kg; injected behind the eyelid under isoflurane anesthesia) prevents leukemia from progressing [3].
In vivo, SKI-178 (20 mg/kg every other day) reduces the number of white blood cells to a normal range and increases survival in an MLL-rearranged AML model. It is a promising therapeutic agent for the treatment of AML, including multidrug-resistant subtypes. Its in vivo efficacy supports its potential for clinical development. Further studies are needed to fully characterize its safety and efficacy profile. |
| Enzyme Assay |
The in vitro enzyme assay for SKI-178 involves measuring its inhibition of SphK1 and SphK2 activity. The enzymes are incubated with varying concentrations of SKI-178 (0.01-10 µM) and the substrate sphingosine in the presence of [γ-33P]ATP. The production of [33P]-S1P is measured, and the IC50 is calculated from dose-response curves. Cell-based assays measure the inhibition of S1P production in cells treated with SKI-178.
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| Cell Assay |
Apoptosis analysis [1]
Cell Types: HL-60 cells Tested Concentrations: 5 μM Incubation Duration: 24 hour Experimental Results: JNK activity (expressed as Thr183/Tyr185 phosphorylation) increased in a time-dependent manner, starting as early as 2 hrs (hours) and continuing to increase At least 24 hrs (hours). Cleavage of caspase-7 indicates a concomitant increase in apoptotic cell death. Bcl-2 Ser70 phosphorylation increased with time of SKI-178 treatment, reaching maximum levels at 8 hrs (hours), consistent with the time of caspase-7 activation. In vitro cellular assays for SKI-178 use AML cell lines, such as MV4-11, MOLM-13, or HL60. Cells are treated with the compound at concentrations of 0.01-10 µM for 24-72 hours. Cell viability is assessed using MTT or CCK-8 assays. Cell cycle analysis is performed by flow cytometry. Apoptosis is evaluated using caspase-3/7 activity assays and Annexin V staining. S1P levels are measured by LC-MS/MS. These assays help characterize its mechanism of action as a sphingosine kinase inhibitor. |
| Animal Protocol |
Animal/Disease Models: MLL-AF9 mouse model (leukemia mouse) [3]
Doses: 20 mg/kg Route of Administration: Retroorbital injection under isoflurane anesthesia; 3 times a week for 1 and 3 weeks Experimental Results: White blood cells (WBC) counts diminished from an initial level of 104 cells/μL and continued to decrease after 3 weeks of treatment until reaching normal levels (~4 × 103 cells/μL). In vivo animal studies for SKI-178 involve mouse xenograft models using human AML cell lines. Tumor-bearing mice are treated with the compound via intraperitoneal injection at doses of 1-30 mg/kg. Tumor volume is measured regularly. White blood cell counts are monitored. Survival is assessed. The compound's effect on tumor growth and leukemia progression is evaluated. Pharmacodynamic studies measure SphK1/2 inhibition and S1P levels in tumor tissues. |
| ADME/Pharmacokinetics |
SKI-178 is a small molecule with a molecular weight of 394.4 and a molecular formula of C21H22N4O4. It is soluble in DMSO and should be stored at -20°C for long-term preservation as a powder and at -80°C in solvent. Its pharmacokinetic properties, including oral bioavailability, half-life, and tissue distribution, are not extensively reported in the available literature. For in vivo studies, it can be formulated in suitable vehicles.
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| References |
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| Additional Infomation |
SKI-178 is a SphK1/SphK2 inhibitor with the CAS number 1259484-97-3. It has IC50 values of 0.1-1.8 µM in various cancer cell lines. It induces prolonged mitosis and apoptosis. It is a novel therapeutic agent for AML, including multidrug-resistant subtypes. The compound is a research tool and is not for human therapeutic use.
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| Molecular Formula |
C21H22N4O4
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|---|---|
| Molecular Weight |
394.431
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| Exact Mass |
394.164
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| Elemental Analysis |
C, 63.95; H, 5.62; N, 14.20; O, 16.22
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| CAS # |
1259484-97-3
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| PubChem CID |
5342941
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| Appearance |
White to off-white solid powder
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| LogP |
3.647
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
565
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O(C)C1=C(C=CC(=C1)C(C)=NNC(C1=CC(C2C=CC(=CC=2)OC)=NN1)=O)OC
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| InChi Key |
GMFUWEBOUKIKRP-LPYMAVHISA-N
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| InChi Code |
InChI=1S/C21H22N4O4/c1-13(15-7-10-19(28-3)20(11-15)29-4)22-25-21(26)18-12-17(23-24-18)14-5-8-16(27-2)9-6-14/h5-12H,1-4H3,(H,23,24)(H,25,26)/b22-13+
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| Chemical Name |
N'-(1-(3,4-Dimethoxyphenyl)ethylidene)-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide InChi Key
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| Synonyms |
SKI 178 SKI-178 SKI178.
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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 (~126.77 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.34 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 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 (6.34 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 25.0 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 | 2.5353 mL | 12.6765 mL | 25.3530 mL | |
| 5 mM | 0.5071 mL | 2.5353 mL | 5.0706 mL | |
| 10 mM | 0.2535 mL | 1.2677 mL | 2.5353 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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