SKI 178 |
Catalog No.GC44896
One-Click Copy Product Info
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SKI 178 is a non-selective inhibitor of Sphingosine Kinases (SphK1 and SphK2).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1259484-97-3
Sample solution is provided at 25 µL, 10mM.
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SKI 178 is a non-selective inhibitor of Sphingosine Kinases (SphK1 and SphK2). SKI 178 competitively binds to the Sph binding site in SphK1, effectively inhibiting Sphingosine-1-Phosphate (S1P) production while inducing intracellular Ceramide (Cer) accumulation and promoting cancer cell apoptosis. SKI 178 exhibits potent cytotoxicity against various cancer cell lines and shows potential in the treatment of solid tumors and hematologic malignancies. SKI 178 also has a microtubule network disrupting effect in vitro and in intact cells[1].
In vitro, SKI 178 (0.08-10µM; 16h) dose‑dependently stabilizes both SphK1 and SphK2 proteins in HEK293 stably overexpresses His6X-SphK1 and His6X-SphK2, with an IC₅₀ of 400-800nM for both[1]. SKI 178 (5µM; 18h) destabilized microtubule polymerization and reduced the rate of tubulin polymerization in HL‑60 cells[1]. SKI 178 (5-25µM; 48-96h) inhibited the viability of primary human prostate cancer cells (PCan1) in a concentration‑ and time‑dependent manner[2]. SKI 178 (5–25µM) dose‑dependently inhibited PCan1 cell proliferation at 48h and cell migration at 16h[2]. SKI 178 (10µM; 72h) showed no significant inhibition of cell viability in RWPE‑1 cells and primary prostate epithelial cells[2]. SKI 178 (10μM; 36h) induced cell cycle arrest and apoptosis in prostatecancer cell[2]. SKI 178 (10µM; 24h) impaired mitochondrial functions in pCan1 primary cells, causing mitochondrial depolarization, ROS production, oxidative injuryand ATP reduction[2].
In vivo, treatment with SKI 178 (20mg/kg; tail vein i.v.; every other day for 1 or 3 weeks) significantly reduced white blood cell counts in the bone marrow of MLL‑AF9 mice, with no observed weight loss or overt toxicity[1]. Retro‑orbital injection of SKI 178 at 20, 10, and 5mg/kg every other day for 1 week reduced white blood cell counts in MLL‑AF9 mice in a dose‑dependent manner[1]. SKI 178 (25mg/kg/d; i.p.; 18d) effectively suppresses PC‑3 xenograft tumor growth in nude mice, concomitantly inhibiting SphK activity and impairing mitochondrial function in tumor tissues, while promoting JNK activation and suppressing the Akt–mTOR pathway[2].
References:
[1] Hengst, Jeremy A et al. “SKI-178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models.” Cancer translational medicine vol. 3,4 (2017): 109-121.
[2] Jin L, Zhu J, Yao L, Shen G, Xue BX, Tao W. Targeting SphK1/2 by SKI-178 inhibits prostate cancer cell growth. Cell Death Dis. 2023;14(8):537. Published 2023 Aug 21.
| Cell experiment [1]: | |
Cell lines | HEK293 stably overexpresses His6X-SphK1 and His6X-SphK2 |
Preparation Method | Nearly confluent 10cm culture dishes of HEK293 cells, overexpressing either His6X-SphK1 or His6X-SphK2, were treated with either vehicle control or 5µM SKI 178 for 16h. After which multiple aliquots of the cell suspension were heated over a temperature gradient (51-63.2℃) that was empirically determined for both SphK1 and SphK2. The presence of SphK1 and SphK2 in the soluble fraction after thermal denaturation was examined by Western blotting. |
Reaction Conditions | 5µM; 16h; 51-63.2℃ |
Applications | Cells treated with SKI 178 show a marked increase in the accumulation of SphK1 and SphK2 protein in the soluble fraction at all temperatures examined, indicating the binding of SKI-178 stabilized SphK1 and SphK2 protein. SKI 178 is instead a non-isoform selective SphK1/2 inhibitor. |
| Animal experiment [1]: | |
Animal models | MLL-AF9 mouse model |
Preparation Method | SKI 178 (20mg/kg) was administered to mice every other day via tail-vein injection in 45% β-HPCD vehicle. Samples were obtained from vehicle treated and SKI 178 treated groups after 1 week and 3 weeks of treatment administration. |
Dosage form | 20mg/kg; every other day for 1 and 3 weeks; tail vein i.v. |
Applications | Among the vehicle treated controls, white blood cell (WBC) counts increased with time from their initial ~104 cells/μL levels to greater than 7×104 cells/μL after 3 weeks of treatment. In contrast, after 1 week of treatment with SKI 178, WBC counts decreased from their initial 104 cells/μL levels and continued to decline after 3 weeks of treatment until they reached normal levels (~4×103 cells/μL). All SKI 178 treated mice were healthy and active. |
References: | |
| Cas No. | 1259484-97-3 | SDF | |
| Canonical SMILES | COC1=C(OC)C=CC(/C(C)=N/NC(C2=CC(C3=CC=C(OC)C=C3)=NN2)=O)=C1 | ||
| Formula | C21H22N4O4 | M.Wt | 394.4 |
| Solubility | DMF: 25 mg/ml,DMSO: 25 mg/ml,DMSO:PBS(pH 7.2) (1:4): 0.2 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.5355 mL | 12.6775 mL | 25.355 mL |
| 5 mM | 507.1 μL | 2.5355 mL | 5.071 mL |
| 10 mM | 253.5 μL | 1.2677 mL | 2.5355 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 13 reference(s) in Google Scholar.)