XST-14

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

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。

XST-14 is a potent, competitive and highly selective ULK1 inhibitor with an IC50 of 26.6 nM. XST-14 induces autophagy inhibition by reducing the phosphorylation of the ULK1 downstream substrate. XST-14 induces apoptosis in hepatocellular carcinoma (HCC) cells and has antitumor effects.

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. XST-14 (20-80 μM; for 24 h) leads a decrease in cell proliferation activity. XST-14 (5 μM; for 24 h) induces apoptosis in HepG2 and human primary HCC cells. XST-14 (5 μM; for 12 h) strongly inhibits the conversion of LC3-I to LC3-II in CHO cells stably expressing GFP-LC3. XST-14 (5 μM; for 12 h) inhibits the Ser249 phosphorylation of PIK3C3 and Ser15 phosphorylation of BECN1. Cell Proliferation Assay Cell Line:HepG2 cells Concentration:20, 40, 60, 80 μM Incubation Time:24 hours Result:Led a decrease in cell proliferation activity. Apoptosis Analysis 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 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 Cell Line:HepG2 cells Concentration:5 μM Incubation Time:12 hours Result:Inhibited the Ser249 phosphorylation of PIK3C3 and Ser15 phosphorylation of BECN1.

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. XST-14 (2 mg/kg for IV; 10 mg/kg for IP) has a T1/2 of 2.31 hours for IV and a T1/2 of 2.69 hours for IP. Animal Model:Nude mice bearing HepG2 tumor xenografts 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 Dosage:2 mg/kg for IV; 10 mg/kg for IP (Pharmacokinetic Analysis Administration: IV or IPResult:Had a T1/2 of 2.31 hours, a CL of 26.28 mL/min?kg, and and an AUC of 1269 hr?ng/mL for IV.

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Autophagy

Autophagy

Autophagy | Apoptosis

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2607143-50-8

291.34

C16H21NO4

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 250 mg/mL (858.10 mM; 超声助溶 )

COC(=O)c1cc2c(OC(C)C)cc(OC(C)C)cc2[nH]1

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(-20℃)

With Ice Pack

≥ 2 years