• 产品描述： 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 agent sensitive and multi-agent 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

• 靶点： SphK1; SphK2

• 体外研究：
  SKI-178 (5 μM; 24 hours)-induced apoptotic cell death correlates with prolonged Bcl-2 phosphorylation. Apoptosis Analysis 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.

• 体内研究：
  SKI-178 (20 mg/kg; retro-orbital injection under isoflurane anesthesia) inhibits leukemic progression in the MLL-AF9 model. Animal Model: MLL-AF9 mouse model (leukemic mice) 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).

• 参考文献：
  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.

• 溶解性： Soluble  in  DMSO

• 保存条件： -20℃

• 配置溶液浓度参考：
  

  	1mg	5mg	10mg
  1 mM	2.535 ml	12.677 ml	25.355 ml
  5 mM	0.507 ml	2.535 ml	5.071 ml
  10 mM	0.254 ml	1.268 ml	2.535 ml
  50 mM	0.051 ml	0.254 ml	0.507 ml

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *