WZH-17-002

WZH-17-002 is a potent, selective PROTAC (proteolysis-targeting chimera) molecule designed to degrade anaplastic lymphoma kinase (ALK) protein, especially targeting compound ALK mutations that are resistant to lorlatinib, such as the G1202R/L1196M mutation. The molecule uses WZH-15-125 as the warhead and employs (methylamino)acetaldehyde as a linker. WZH-17-002 demonstrates a half maximal degradation concentration (DC50) of 25 nM in relevant cell models, shows anti-proliferative activity, and exhibits superior in vivo efficacy compared to lorlatinib in ALK G1202R/L1196M xenograft mouse models. Its primary development aim is to overcome resistance to ALK tyrosine kinase inhibitor therapies in non-small cell lung cancer (NSCLC)[4][7][1][3][10].