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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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SKI-178 is a sphingosine kinase 1 (SphK1) inhibitor (IC50 = 0.1-1.8 μM) which is a novel therapeutic agent for the treatment of AML, including multidrug-resistant/recurrent AML subtypes.
| ln Vitro |
Prolonged Bcl-2 phosphorylation is linked to liver cancer cell mortality mediated by SKI-178 (5 μM; 24 hours) [1].
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| ln Vivo |
In the MLL-AF9 model, SKI-178 (20 mg/kg; injected behind the eyelid under isoflurane anesthesia) prevents leukemia from progressing [3].
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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. |
| 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). |
| References |
[1]. Hengst JA, et al. SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models. Cancer Transl Med. 2017;3(4):109-121.
[2]. Hengst JA, et al. Development of a sphingosine kinase 1 specific small-molecule inhibitor. Bioorg Med Chem Lett. 2010;20(24):7498-7502. [3]. Dick TE, et al. The apoptotic mechanism of action of the sphingosine kinase 1 selective inhibitor SKI-178 in human acute myeloid leukemia cell lines. J Pharmacol Exp Ther. 2015;352(3):494-508. |
| Molecular Formula |
C21H22N4O4
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|---|---|
| Molecular Weight |
394.431
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| Exact Mass |
394.1641
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| CAS # |
1259484-97-3
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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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| 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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| 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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