JX06 是一种有效的,选择性的,共价的PDK抑制剂。JX06 抑制PDK1,PDK2和PDK3,IC50值分别为 49 nM,101 nM 和 313 nM。JX06 以不可逆的方式与半胱氨酸残基共价结合来抑制PDK1活性。JX06 具有抗肿瘤活性。
生物活性 | JX06 is a potent, selective and covalent inhibitor ofPDK. JX06 inhibitsPDK1,PDK2andPDK3withIC50s of 49 nM, 101 nM, and 313 nM, respectively. JX06 inhibits PDK1 activity via covalently binding to a cysteine residue in an irreversible manner. JX06 shows significant antitumor activity[1]. |
IC50& Target | IC50: 49 nM (PDK1), 101 nM (PDK2), 313 nM (PDK3)[1] |
体外研究 (In Vitro) | JX06 barely shows inhibitory activity against PDK4 at a concentration of 10 μM[1]. JX06 (1-10 μM; 48 hours) induces cell apoptosis in cancer cells with high ECAR/OCR[1]. JX06 (0-0.6 μM; 72 hours) dose-dependently suppresses the growth of A549 cells[1]. JX06 (0.1-10 μM; 6-24 hours) inhibits PDHA1 phosphorylation in A549 cells in a time- and dose-dependent manner[1]. JX06 (1-10 μM) increases glucose uptake and intracellular ATP level and reduces aerobic glycolysis determined by the lactate production in A549 cells[1]. JX06 (1-10 μM; 24 hours) induces ROS generation in cancer cells with high extracellular acidification rate (ECAR)/ oxygen consumption rate (OCR)[1].
Apoptosis Analysis[1] Cell Line: | A549, EBC-1, HT-29 and H460 cells | Concentration: | 0, 1, 3, 10 μM | Incubation Time: | 48 hours | Result: | Induces cell apoptosis in A549 and EBC-1 cells. |
Cell Viability Assay[1] Cell Line: | A549 cells | Concentration: | 0, 0.2, 0.4, 0.6 μM | Incubation Time: | 72 hours | Result: | Inhibits the viability of A549 cells in a dose dependent manner. |
Western Blot Analysis[1] Cell Line: | A549 cells | Concentration: | 0, 0.1, 0.3, 1, 3, 10 μM | Incubation Time: | 0, 6, 12, 24 hours | Result: | Decreased PDHA1 phosphorylation at both serine 293 and serine 232 (S293 and S232) in a time- and dose-dependent manner. |
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体内研究 (In Vivo) | JX06 (40-80 mg/kg; i.p. for 21 days) inhibits tumor growth in vivo[1].
Animal Model: | A549 subcutaneous xenograft mice[1] | Dosage: | 40, 80 mg/kg | Administration: | I.p. injections for 21 days | Result: | Reduced tumor weights and 67.5% tumor volume at the dose of 80 mg/kg compared with the vehicle control. Well tolerated at the administration dose. |
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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(154.08 mM;Need ultrasonic) 配制储备液 1 mM | 3.0816 mL | 15.4078 mL | 30.8157 mL | 5 mM | 0.6163 mL | 3.0816 mL | 6.1631 mL | 10 mM | 0.3082 mL | 1.5408 mL | 3.0816 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 (7.70 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (7.70 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 (7.70 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (7.70 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。 3. 请依序添加每种溶剂: 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (7.70 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (7.70 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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