ZX-29

Modify Date: 2024-04-03 04:57:05

ZX-29 Structure
ZX-29 structure
Common Name ZX-29
CAS Number 2254805-62-2 Molecular Weight 518.03
Density N/A Boiling Point N/A
Molecular Formula C23H28ClN7O3S Melting Point N/A
MSDS N/A Flash Point N/A

 Use of ZX-29


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].

 Names

Name ZX-29

 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

[1]. Gou W, et al. ZX-29, a novel ALK inhibitor, induces apoptosis via ER stress in ALK rearrangement NSCLC cells and overcomes cell resistance caused by an ALK mutation. Biochim Biophys Acta Mol Cell Res. 2020 Mar 26;1867(7):118712.

 Chemical & Physical Properties

Molecular Formula C23H28ClN7O3S
Molecular Weight 518.03