SKI-178 是一种有效的鞘氨醇激酶-1(SphK1)和SphK2抑制剂。SKI-178 对药物敏感和多药耐药癌细胞系 (如MTR3、NCI-ADR 和 HL60/VCR) 的 IC50浓度范围为 1.8 到 0.1 μM。SKI-178 以 CDK1 依赖性方式诱导人急性髓性白血病细胞凋亡。
| 生物活性 | SKI-178 is a potentsphingosine kinase-1 (SphK1)andSphK2inhibitor. SKI-178 is cytotoxic at IC50concentrations ranging from 1.8 to 0.1 μM in both drug sensitive and multi-drug resistantcancercell lines (i.e., MTR3, NCI-ADR and HL60/VCR cells). SKI-178 inducesapoptosisin a CDK1-dependent manner in human acute myeloid leukemia cell lines[1][2]. |
体外研究
(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. |
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体内研究
(In Vivo) | SKI-178 (20 mg/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). |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 50 mg/mL(126.77 mM;Need ultrasonic) 配制储备液 | 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 |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: 2.5 mg/mL (6.34 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (6.34 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (6.34 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.34 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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