NUV-244

NUV-244 is a potent and selective small-molecule degrader of the patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M variant. The I148M mutation is a well-established genetic determinant of fatty liver disease and has emerging implications in cancer biology, particularly in metabolic reprogramming and hepatocellular carcinoma (HCC). NUV-244 functions by inducing the targeted degradation of the PNPLA3 I148M protein, serving as a pharmacological tool to investigate the oncogenic and tumor-modulatory roles of this variant. Preclinical studies have demonstrated that NUV-244 treatment can modulate cancer cell transcriptomics, proteomics, mitochondrial function, and survival, highlighting its potential to create selective vulnerabilities in cancer cells with metabolic plasticity.