[CAS NO. 1259484-97-3] SKI-178
PRODUCTS SPECIFICATIONS [1259484-97-3]
DESCRIPTION [1259484-97-3]
Overview
| MDL | - |
|---|---|
| Molecular Weight | 394.42 |
| Molecular Formula | C21H22N4O4 |
| SMILES | O=C(C1=CC(C2=CC=C(OC)C=C2)=NN1)N/N=C(C3=CC=C(OC)C(OC)=C3)\C |
Summary
SKI-178 is a potent sphingosine kinase-1 (SphK1) and SphK2 inhibitor. SKI-178 is cytotoxic at IC 50 concentrations ranging from 1.8 to 0.1 μM in both drug sensitive and multi-drug resistant cancer cell lines (i.e., MTR3, NCI-ADR and HL60/VCR cells). SKI-178 induces apoptosis in a CDK1-dependent manner in human acute myeloid leukemia cell lines [1] [2] .
In Vitro
SKI-178 (5 μM; 24 hours)-induced apoptotic cell death correlates with prolonged Bcl-2 phosphorylation [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Apoptosis Analysis [1]
| Cell Line: | HL-60 cells |
| Concentration: | 5 μM |
| Incubation Time: | 24 hours |
| Result: | JNK activity (indicated by phosphorylation at Thr183/Tyr185) increased in a time-dependent manner starting as early as 2 hours continued to increase for at least 24 hours. There was a concomitant increase in apoptotic cell death indicated by the cleavage of caspase-7. Bcl-2 phosphorylation at Ser70 increased with time in response to SKI-178 treatment, reaching maximal levels at 8 hours, which was consistent with the timing of caspase-7 activation. |
In Vivo
SKI-178 (20 mg/kg; retro-orbital injection under isoflurane anesthesia) inhibits leukemic progression in the MLL-AF9 model [3] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | MLL-AF9 mouse model (leukemic mice) [3] |
| Dosage: | 20 mg/kg |
| Administration: | Retro-orbital injection under isoflurane anesthesia; three times per week for 1 and 3 weeks |
| Result: | White blood cell (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). |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 50 mg/mL ( 126.77 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.5354 mL | 12.6768 mL | 25.3537 mL |
| 5 mM | 0.5071 mL | 2.5354 mL | 5.0707 mL |
| 10 mM | 0.2535 mL | 1.2677 mL | 2.5354 mL |
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Add each solvent one by one: 10% DMSO >> 90% corn oil
Solubility: ≥ 2.5 mg/mL (6.34 mM); Clear solution
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.