XST-14 是一种有效的，竞争性强且高度选择性的ULK1抑制剂，IC50为 26.6 nM。XST-14 通过减少 ULK1 下游底物的磷酸化来诱导自噬抑制。XST-14 诱导肝细胞癌 (HCC) 细胞凋亡，并具有抗肿瘤作用。
| 生物活性 | XST-14 is a potent, competitive and highly selectiveULK1inhibitor with anIC50of 26.6 nM. XST-14 inducesautophagyinhibition by reducing the phosphorylation of theULK1downstream substrate. XST-14 inducesapoptosisin hepatocellular carcinoma (HCC) cells and has antitumor effects[1]. |
| IC50& Target[1] | CaMK II | ULK1 26.6 nM (IC50) |
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体外研究
(In Vitro) | XST-14 inhibits ULK1 (IC50=13.6 nM), MAP2K1/MEK1 (IC50=721.8 nM), MAPK14/p38 alpha (IC50=283.9 nM), TGFBR2 (IC50=809.3 nM), ACVR1/ALK2 (IC50=183.8 nM), ULK2 (IC50=70.9 nM) and CAMK2A (IC50=66.3 nM) by the 10-point titration results from SelectScreen Kinase Profiling Services[1].
XST-14 (20-80 μM; for 24 h) leads a decrease in cell proliferation activity[1].
XST-14 (5 μM; for 24 h) induces apoptosis in HepG2 and human primary HCC cells[1].
XST-14 (5 μM; for 12 h) strongly inhibits the conversion of LC3-I to LC3-II in CHO cells stably expressing GFP-LC3[1].
XST-14 (5 μM; for 12 h) inhibits the Ser249 phosphorylation of PIK3C3 and Ser15 phosphorylation of BECN1[1].
Cell Proliferation Assay[1] | Cell Line: | HepG2 cells | | Concentration: | 20, 40, 60, 80 μM | | Incubation Time: | 24 hours | | Result: | Led a decrease in cell proliferation activity. |
Apoptosis Analysis[1] | Cell Line: | HepG2 and human primary cells | | Concentration: | 5 μM | | Incubation Time: | 24 hours | | Result: | Induced apoptosis in HepG2 and human primary HCC cells. |
Cell Autophagy Assay[1] | Cell Line: | CHO, HepG2 cells stably expressing GFP-LC3 | | Concentration: | 5 μM | | Incubation Time: | 12 hours | | Result: | Strongly inhibited the conversion of LC3-I to LC3-II in CHO cells.
Dramatically decreased the number of GFP-LC3 puncta in HepG2 cells.
Decreased autophagosome formation and blocked autophagosome/lysosome fusion in HepG2 cells. |
Western Blot Analysis[1] | Cell Line: | HepG2 cells | | Concentration: | 5 μM | | Incubation Time: | 12 hours | | Result: | Inhibited the Ser249 phosphorylation of PIK3C3 and Ser15 phosphorylation of BECN1. |
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体内研究
(In Vivo) | XST-14 (15, 30 mg/kg/day; IP; for 4 consecutive weeks) displays anti-HCC efficacies, resulting in decreased tumor weights and suppressed tumor growth of HCC cells in nude mice[1].
XST-14 (2 mg/kg for IV; 10 mg/kg for IP) has a T1/2of 2.31 hours for IV and a T1/2of 2.69 hours for IP[1].
| Animal Model: | Nude mice bearing HepG2 tumor xenografts[1] | | Dosage: | 15, 30 mg/kg | | Administration: | IP; daily; for 4 consecutive weeks | | Result: | Displayed anti-HCC efficacies, resulting in decreased tumor weights and suppressed tumor growth of HCC cells in nude mice. |
| Animal Model: | Sprague-Dawley rat[1] | | Dosage: | 2 mg/kg for IV; 10 mg/kg for IP (Pharmacokinetic Analysis) | | Administration: | IV or IP | | Result: | Had a T1/2of 2.31 hours, a CL of 26.28 mL/minokg, and and an AUC of 1269 hrong/mL for IV.
Had a T1/2of 2.69 hours, a Cmaxof 2033 ng/mL, and an AUC of 5979 hrong/mL for IP. |
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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 : 250 mg/mL(858.10 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.4324 mL | 17.1621 mL | 34.3242 mL | | 5 mM | 0.6865 mL | 3.4324 mL | 6.8648 mL | | 10 mM | 0.3432 mL | 1.7162 mL | 3.4324 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 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.08 mg/mL (7.14 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (7.14 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 20.8 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。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.08 mg/mL (7.14 mM); Clear solution
此方案可获得 ≥ 2.08 mg/mL (7.14 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 20.8 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。 |
