生物活性 | PIK-75 hydrochloride is a reversibleDNA-PKandp110α-selective inhibitor, which inhibitsDNA-PK,p110αand p110γ withIC50s of 2, 5.8 and 76 nM, respectively. PIK-75 hydrochloride inhibits p110α >200-fold more potently than p110β (IC50=1.3 μM)[1][2]. PIK-75 hydrochloride inducesapoptosis[3]. |
IC50& Target[1] | DNA-PK 2 nM (IC50) | p110α 5.8 nM (IC50) | p110γ 76 nM (IC50) | p110δ 510 nM (IC50) | p110β 1.3 μM (IC50) | hsVPS34 2.6 μM (IC50) | PI3KC2β 1 μM (IC50) | PI3KC2α 10 μM (IC50) | mTORC1 1 μM (IC50) | mTORC2 10 μM (IC50) | ATM 2.3 μM (IC50) | ATR 21 μM (IC50) | PI4KIIIβ 50 μM (IC50) |
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体外研究 (In Vitro) | PIK-75 also inhibits p110δ, PI3KC2β, mTORC1, ATM, hsVPS34, PI3KC2α, mTORC2, ATR and PI4KIIIβ with IC50s of 510 nM, ~1 μM, ~1 μM, 2.3 μM, 2.6 μM, ~10 μM, ~10 μM, 21 μM, ~50 μM, respectively[1]. PIK-75 alone blocks Thr 308 phosphorylation in L6 myotubes and 3T3-L1 adipocytes with IC50values of 1.2 and 1.3 μM, respectively[1]. PIK-75 (1-1000 nM; 5 min) blocks the phosphorylation of PKB induced by insulin on both Ser473and Thr308 in CHO-IR cells in a dose-dependent manner, with an IC50of 78 nM[2]. PIK-75 (0.1-1000 nM; 48 hours) inhibits the proliferation and survival of pancreatic cancer cells through apoptotic cell death[3]. PIK-75 (0.1-1000 nM) also reduces the colony formation of pancreatic cancer MIA PaCa-2 and AsPC-1 cells[3].
Cell Viability Assay[3] Cell Line: | Human pancreatic cancer cells (MIA PaCa-2 or AsPC-1) | Concentration: | 0.1, 0.3, 1, 3, 10, 30, 100, 300, and 1000 nM | Incubation Time: | 48 hours | Result: | Submicromolar concentration was sufficient to inhibit the proliferation of pancreatic cancer, MIA PaCa-2 and AsPC-1 cells after 48-h treatment. |
Western Blot Analysis[2] Cell Line: | Overnight-starved CHO-IR cells | Concentration: | 1, 10, 100, 1000 nM | Incubation Time: | 5 minutes | Result: | Blocked the phosphorylation of PKB induced by insulin (1 nM, 10 min) on both Ser473and Thr308 in a dose-dependent manner. |
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体内研究 (In Vivo) | PIK-75 (2 mg/kg) potentiates anticancer activity of Gemcitabine (20 mg/kg) in vivo. Gemcitabine (20 mg/kg) or PIK-75 (2 mg/kg) alone reduces the tumor growth to similar degree. Beneficial effect of PIK-75/Gemcitabine is evident as this combination markedly reduces the tumor growth in vivowithout affecting the body weights of mice[3].
Animal Model: | Mice bearing tumors of MIA PaCa-2[3] | Dosage: | 2 mg/kg; or combination with Gemcitabine (20 mg/kg) | Administration: | Administered injection; 5 times per week. 25 days | Result: | Reduced the tumor growth and enhanced the antitumor effect. |
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运输条件 | Room temperature in continental US; may vary elsewhere. |
储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
溶解性数据 | In Vitro: DMSO : 11 mg/mL(22.51 mM;Need ultrasonic) H2O :< 0.1 mg/mL (ultrasonic;warming;heat to 60℃)(insoluble) 配制储备液 1 mM | 2.0461 mL | 10.2304 mL | 20.4608 mL | 5 mM | 0.4092 mL | 2.0461 mL | 4.0922 mL | 10 mM | 0.2046 mL | 1.0230 mL | 2.0461 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 (sealed storage, away from moisture)。-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: ≥ 1.1 mg/mL (2.25 mM); Clear solution
此方案可获得 ≥ 1.1 mg/mL (2.25 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 11.0 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: ≥ 1.1 mg/mL (2.25 mM); Clear solution
此方案可获得 ≥ 1.1 mg/mL (2.25 mM,饱和度未知) 的澄清溶液。 以 1 mL 工作液为例,取 100 μL 11.0 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。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 1.1 mg/mL (2.25 mM); Clear solution
此方案可获得 ≥ 1.1 mg/mL (2.25 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 11.0 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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