Discovery of Novel MLKL PROTAC Degraders for the Treatment of Hepatocellular Carcinoma via Promoting Parthanatos - PubMed
3 hours ago
- #Parthanatos
- #MLKL Degrader
- #Hepatocellular Carcinoma
- Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths due to low immunogenicity and immunosuppressive tumor microenvironment.
- Immunogenic cell death (ICD) is a promising anticancer strategy that enhances tumor immunogenicity and activates immune responses.
- MLKL is a key effector in necroptosis, but its non-necroptotic functions are understudied.
- C116, a novel MLKL degrader, was discovered using AI-assisted ligand discovery and protein degradation technology.
- C116 induces MLKL degradation and promotes parthanatos in HCC cells, showing strong antitumor effects in vivo.
- C116 is a potential therapeutic candidate for HCC and for studying MLKL's non-necroptotic roles.