SKI V 是一种非竞争性的，有效的非脂质鞘氨醇激酶 (SPHK; SK) 抑制剂，对 GST-hSK 的IC50为 2 μM。 SKI V 有效抑制PI3K，对 hPI3k 的IC50为 6 μM。SKI V 减少有丝分裂的第二信使鞘氨醇-1-磷酸 (S1P) 的形成。SKI V 诱导细胞凋亡 (apoptosis) 并具有抗肿瘤活性。
| 生物活性 | SKI V is a noncompetitive and potent non-lipidsphingosine kinase (SPHK; SK)inhibitor with anIC50of 2 μM for GST-hSK. SKI V potently inhibitsPI3Kwith anIC50of 6 μM for hPI3k. SKI V decreases formation of the mitogenic second messenger sphingosine-1-phosphate (S1P). SKI V inducesapoptosisand has antitumor activity[1][2]. |
| IC50& Target | IC50: 2 μM (GST-hSK), 6 μM (hPI3k) and 80 μM (ERK2)[1] |
体外研究
(In Vitro) | SKI V has weak activity toward ERK2 (IC50of 80 μM for hERK2) and does not inhibit PKC-α[1].
SKI V (10 μM; for 24 hours) inhibits cancer cell proliferation and induces apoptosis[1].
SKI V (0.2, 1, 5 μM; pretreated for 1 hour) decreases phospho-Akt and phospho-MEK levels. Near-confluent cultures of JC cells are serum-starved for 16 hours, followed by pretreatment SKI V for 1 hour[2].
SKI V has IC50s for inhibition of sphingosine kinase (SK) and tumor cell proliferation of ~2 μM[1].
SKI V (20 μg/ml) inhibits not only purified but endogenous SK in in MDA-MB-231 cells[1].
SKI V (0.2, 1, 5 μM) inhibits intracellular S1P formation in JC cells in a dose-dependent fashion[2].
Cell Proliferation Assay[1] | Cell Line: | T24 tumor cells | | Concentration: | 10 μM | | Incubation Time: | For 24 hours | | Result: | Inhibited cancer cell proliferation. |
Apoptosis Analysis[1] | Cell Line: | T24 tumor cells | | Concentration: | 10 μM | | Incubation Time: | For 24 hours | | Result: | Induced apoptosis. |
Western Blot Analysis[2] | Cell Line: | JC cells | | Concentration: | 0.2, 1, 5 μM | | Incubation Time: | Pretreated for 1 hour | | Result: | Decreased phospho-Akt and phospho-MEK levels. |
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体内研究
(In Vivo) | SKI V (75 mg/kg; i.p.; days 1, 5, 9, 15) significantly lowers tumor growth (>50% decreased at day 18) than control animals[1].
| Animal Model: | 6-8 weeks old BALB/c female mice with JC mammary adenocarcinoma cells[1] | | Dosage: | 75 mg/kg | | Administration: | IP; days 1, 5, 9, 15 | | Result: | Tumor growth was significantly lower (>50% decreased at day 18) than tumor growth in control animals. |
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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 | | 4°C | 2 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(196.66 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.9333 mL | 19.6665 mL | 39.3329 mL | | 5 mM | 0.7867 mL | 3.9333 mL | 7.8666 mL | | 10 mM | 0.3933 mL | 1.9666 mL | 3.9333 mL |
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以下溶剂前显示的百
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此方案可获得 ≥ 2.5 mg/mL (9.83 mM，饱和度未知) 的澄清溶液。 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% (20%SBE-β-CDin saline) Solubility: 2.5 mg/mL (9.83 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (9.83 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 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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