ZX-29 是一种有效的选择性的 ALK 抑制剂，对 ALK，ALK L1196M 和 ALK G1202R 的 IC50 分别为 2.1 nM，1.3 nM 和 3.9 nM，但对 EGFR 无活性。ZX-29 通过诱导内质网应激来诱导细胞凋亡 (apoptosis)，并克服了由 ALK 突变引起的细胞抗性。ZX-29 还可诱导保护性自噬 (autophagy) 并具有抗肿瘤作用。
货号:ajcx36798
CAS:2254805-62-2
分子式:C23H28ClN7O3S
分子量：518.03
溶解度:DMSO : 50 mg/mL (96.52 mM; ultrasonic and warming and heat to 60°C)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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].

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].

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].

[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.