In the realm of drug discovery, PROTAC technology has recently garnered attention as a novel therapeutic approach. Functioning as a heterobifunctional molecule, PROTAC comprises two ligands, each responsible for recruiting the target protein and E3 ligase, respectively. To target the anaplastic lymphoma kinase (ALK) fusion proteins, such as NPM-ALK or EML4-ALK, Chung devised various ALK-PROTAC molecules incorporating ceritinib, an ALK inhibitor, and the ligand of von Hippel-Lindau (VHL) E3 ligase. Among these compounds, TD-004 demonstrated effective induction of ALK degradation and inhibited the growth of ALK fusion-positive cell lines, SU-DHL-1, and H3122. Additionally, we validated that TD-004 significantly reduced tumor growth in the H3122 xenograft model.
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