ZX-29
Names
[ CAS No. ]:
2254805-62-2
[ Name ]:
ZX-29
Biological Activity
[Description]:
ZX-29 is a potent and selective ALK inhibitor with an IC50 of 2.1 nM, 1.3 nM and 3.9 nM for ALK, ALK L1196M and ALK G1202R mutations, respectively. ZX-29 is inactive against EGFR. ZX-29 induces apoptosis by inducing endoplasmic reticulum (ER) stress and overcomes cell resistance caused by an ALK mutation. ZX-29 also induces protective autophagy and has antitumor effect[1].
[Related Catalog]:
[Target]
IC50: 2.1 nM (ALK), 1.3 nM (ALK L1196M) and 3.9 nM (ALK G1202R)[1]
[In Vitro]
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[1]. 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[1]. ZX-29 (10 nM; 0-48 hours; NCI-H2228 cells) inhibits the proliferation of NCI-H2228 cells and arrests the cells in G1 phase[1]. 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[1]. 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[1]. ZX-29 (20 nM; 0-48 hours; NCI-H2228 cells) treatment significantly increases the mRNA level of CHOP[1]. 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[1]. Cell Viability Assay[1] 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[1] 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[1] 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[1] 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 Analysis[1] Cell 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-PCR[1] Cell Line: NCI-H2228 cells Concentration: 20 nM Incubation Time: 0 hour, 6 hours, 12 hours, 24 hours or 48 hours Result: The mRNA level of CHOP was increased significantly.
[In Vivo]
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[1]. Animal Model: Female BALB/c nude mice (4-week-old) with H2228 cells[1] Dosage: 50 mg/kg Administration: Intragastric administration; every 2 days; for a total of 7 times Result: Showed significantly attenuated tumor growth.
[References]
Chemical & Physical Properties
[ Molecular Formula ]:
C23H28ClN7O3S
[ Molecular Weight ]:
518.03