ZX-29

Research use only, not for human use.

ZX-29 is a potent and selective inhibitor of ALK, and also induces protective autophagy and has antitumor effect.

ZX-29 is a potent and selective inhibitor of ALK(IC50 of 2.1 nM, 1.3 nM and 3.9 nM for ALK, ALK L1196M and ALK G1202R mutations, respectively), and also induces protective autophagy and has antitumor effect.(In Vitro):ZX-29 dose-dependently inhibits colony formation of NCI-H2228 cells. With an increase in ZX-29 concentration, the cell density decreased gradually, and the cells lost their normal morphology and become sharp and slender. In NCI-H2228 cells, ZX-29 (10 nM; 0-48 hours) inhibits the proliferation of and arrests the cells in G1 phase. ZX-29 (0-81 nM; 24-72 hours) treatment resulted in a decrease in the viability with time and dose. ZX-29 (10 nM; 24 hours) treatment causes typical signs of autophagy and the formation of autophagosomes and enhances the expression level of LC3 and Beclin1. ZX-29 (20 nM; 0-48 hours) treatment significantly increases the mRNA level of CHOP. (In Vivo):In a mouse xenograft model, ZX-29 treatment suppresses tumor growth.

ZX-29 (0-81 nM; 24-72 hours; NCI-H2228 cells) treatment leads to a time- and dose-dependent decrease in NCI-H2228 cell viability.ZX-29 (10 nM; 24 hours; NCI-H2228 cells) treatment causes typical signs of autophagy and the formation of autophagosomes. ZX-29 enhances the expression level of LC3 and Beclin1.ZX-29 (10 nM; 0-48 hours; NCI-H2228 cells) inhibits the proliferation of NCI-H2228 cells and arrests the cells in G1 phase.ZX-29 (10-40 nM; 24-48 hours; NCI-H2228 cells) treatment induces apoptosis of NCI-H2228 cells. ZX-29 dose-dependently upregulates the expression levels of proapoptotic protein Bax, increases the production of activated forms of caspase 3, and downregulates the expression level of antiapoptotic protein Bcl-2.ZX-29 (30-300 nM; 24 hours; NCI-H2228 cells) treatment significantly down-regulates the expression of p-ALK and its downstream signaling proteins, including p-Akt and p-STAT3, in a dose-dependent manner.ZX-29 (20 nM; 0-48 hours; NCI-H2228 cells) treatment significantly increases the mRNA level of CHOP.ZX-29 dose-dependently inhibits colony formation of NCI-H2228 cells. With an increase in ZX-29 concentration, the cell density decreased gradually, and the cells lost their normal morphology and become sharp and slender. Cell Viability Assay Cell Line:NCI-H2228 cells Concentration:0 nM, 1 nM, 3 nM, 9 nM, 10 nM, 27 nM or 81 nM Incubation Time:24 hours, 48 hours or 72 hours Result:Led to a time- and dose-dependent decrease in NCI-H2228 cell viability. Cell Autophagy Assay Cell Line:NCI-H2228 cells Concentration:10 nM Incubation Time:24 hours Result:Caused typical signs of autophagy and the formation of autophagosomes.Cell Cycle Analysis Cell Line:NCI-H2228 cells Concentration:0 hour, 12 hours, 24 hours or 48 hours Incubation Time:24 hours Result:Arrested the NCI-H2228 cells in G1 phase in a time-dependent manner.Apoptosis Analysis Cell Line:NCI-H2228 cells Concentration:10 nM, 20 nM or 40 nM Incubation Time:24 hours, 48 hours Result:Promoted NCI-H2228 cell apoptosis in a dose-dependent manner.Western Blot AnalysisCell Line:NCI-H2228 cells Concentration:30 nM, 100 nM, 300 nM Incubation Time:24 hours Result:Significantly down-regulated the expression of p-ALK and its downstream signaling proteins, including p-Akt and p-STAT3, in a dose-dependent manner. RT-PCRCell Line:NCI-H2228 cells Concentration:20 nM Incubation Time:0 hour, 6 hours, 12 hours, 24 hours or 48 hoursResult:The mRNA level of CHOP was increased significantly.

ZX-29 (50 mg/kg; intragastric administration; every 2 days; for a total of 7 times; female BALB/c nude mice) treatment suppresses tumor growth in a mouse xenograft model. Animal Model:Female BALB/c nude mice (4-week-old) with H2228 cells Dosage:50 mg/kg Administration:Intragastric administration; every 2 days; for a total of 7 times Result:Showed significantly attenuated tumor growth.

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Angiogenesis

ALK

Dnm1 GTPase

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2254805-62-2

518.03

C23H28ClN7O3S

>98% (HPLC)

In Vitro:?DMSO : 50 mg/mL (96.52 mM)

COc1cc(ccc1Nc1ncc(Cl)c(Nc2ccccc2NS(C)(=O)=O)n1)N1CCN(C)CC1

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(-20℃)

With Ice Pack

≥ 2 years