OSU-T315 是整联蛋白连接激酶 (ILK) 的抑制剂 (IC50=0.6 μM), 通过去磷酸化 AKT-Ser473 和其他 ILK 靶标 (GSK-3β和肌球蛋白轻链) 抑制 PI3K/AKT 信号传导。
OSU-T315 阻止 AKT 转位到脂筏消除 AKT 的活化，并以 ILK 非依赖性方式触发 Caspase 依赖性细胞凋亡 (Apoptosis)。OSU-T315 通过自噬 (Autophagy) 和凋亡 (Apoptosis) 导致细胞死亡。
| 生物活性 | OSU-T315 (ILK-IN-1) is a small Integrin-linked kinase(ILK)inhibitor with an IC50of 0.6 μM, inhibiting PI3K/AKT signaling by dephosphorylation of AKT-Ser473 and other ILK targets (GSK-3β andmyosinlight chain)[1]. OSU-T315 abrogatesAKTactivation by impedingAKTlocalization in lipid rafts and triggers caspase-dependentapoptosisin an ILK-independent manner[2]. OSU-T315 causes cell death throughapoptosisandautophagy[1]. |
| IC50& Target | IC50: 0.6μM; Integrin-linked kinase (ILK) inhibitor[1] |
体外研究
(In Vitro) | OSU-T315 (Compound 22; 0-5 μM; 24 hours) exhibits high in vitro potency against a panel of prostate and breast cancer cell lines with a IC50range of 1-2.5 μM[1].
OSU-T315 (0-2.5 μM; 24 hours) can reduce YB-1, HER2, and EGFR expression; shows a modest suppressive effect on phosphorylated S6 levels, exhibits dose-dependent suppressive effects on the levels of phospho-ERK1/2 and phospho-p38, while that of phospho-JNK remains unaltered in PC-3 cell[1].
OSU-T315 (0-4 μM; 24 hours) causes autophagy through ILK inhibition[1].
Western Blot Analysis[1] | Cell Line: | PC-3 cells; MDA-MB-231 cells | | Concentration: | 1 μM, 2 μM, 3 μM, 4 μM; 0.5 μM, 1 μM, 1.5 μM, 2 μM, 2.5 μM | | Incubation Time: | 24 hours | | Result: | Exhibited a dose-dependent decreasing effect on the phosphorylation of pS6, ERKs, and p38 in PC-3 cells and MDA-MB-231 cells. |
Cell Viability Assay[1] | Cell Line: | Prostate cancer cells: LNCaP, PC-3; breast cancer cells: MDA-MB-231, MDA-MB-468, SKBR3, MCF-7; PrEC and MEC cells | | Concentration: | 0-5 μM | | Incubation Time: | 24 hours | | Result: | Suppressed cancer cells viability in breast and prostate cancer cells (IC (50), 1-2.5μM). |
Apoptosis Analysis[1] | Cell Line: | PC-3 cells | | Concentration: | 1 μM, 2 μM, 3 μM, 4 μM | | Incubation Time: | 24 hours | | Result: | Induced accumulation of LC3-II and PARP cleavage. |
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体内研究
(In Vivo) | OSU-T315 (Oral gavage; 25 mg/kg, 50 mg/kg; single daily; 35 days) has a suppressive effect of on PC-3 xenograft tumor growth[1].
No other obvious toxicity is observed in mice[1].
| Animal Model: | Male NCr athymic nude mice with PC-3 tumor xenografts | | Dosage: | 25 mg/kg; 50 mg/kg | | Administration: | Oral gavage; single daily; 35 days | | Result: | Resulted in suppression of tumor growth relative to the vehicle control after 35 days of treatment (48% and 62% suppression for 25 and 50 mg/kg, respectively). |
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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 : ≥ 260 mg/mL(487.27 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 1.8741 mL | 9.3705 mL | 18.7410 mL | | 5 mM | 0.3748 mL | 1.8741 mL | 3.7482 mL | | 10 mM | 0.1874 mL | 0.9370 mL | 1.8741 mL |
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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: ≥ 2.17 mg/mL (4.07 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (4.07 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 21.7 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: ≥ 2.17 mg/mL (4.07 mM); Clear solution
此方案可获得 ≥ 2.17 mg/mL (4.07 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 21.7 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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