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| Cas No.: | 1259484-97-3 |
| Chemical Name: | N'-(1-(3,4-Dimethoxyphenyl)ethylidene)-3-(4-methoxyphenyl)-1H-pyrazole-5-carbohydrazide |
| SMILES: | COC1C=C(C(=NNC(C2NN=C(C3C=CC(OC)=CC=3)C=2)=O)C)C=CC=1OC |
| Formula: | C21H22N4O4 |
| M.Wt: | 394.423784732819 |
| Purity: | >98% |
| Sotrage: | 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO |
| Description: | SKI-178 is a potent sphingosine kinase-1 (SphK1) and SphK2 inhibitor. SKI-178 is cytotoxic at IC50 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). SKI-178 induces apoptosis in a CDK1-dependent manner in human acute myeloid leukemia cell lines[1][2]. |
| In Vivo: | SKI-178 (20mg/kg; retro-orbital injection under isoflurane anesthesia) inhibits leukemic progression in the MLL-AF9 model[3]. 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). |
| In Vitro: | SKI-178 (5 μM; 24 hours)-induced apoptotic cell death correlates with prolonged Bcl-2 phosphorylation[1]. 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. |
| 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. |
MSDS
COA
| LOT NO. | DOWNLOAD |
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| 2018-0101 |
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| 2018-0101 |
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| 2018-0101 |
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