ZX-29 is a potent and selective inhibitor of ALK with IC50 values of 2.1 nM, 1.3 nM, and 3.9 nM for ALK, ALK [L1196M], and ALK [G1202R] mutations, respectively. It also induces protective autophagy and exhibits antitumor effects.

ALK (F1196M):1.3 nM , ALK (G1202R):3.9 nM , ALK:2.1 nM

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[1].

In a mouse xenograft model, ZX-29 treatment suppresses tumor growth[1].