Lipistad

Lipistad is a liposomal formulation of disulfiram, an aldehyde dehydrogenase (ALDH) inhibitor traditionally used to treat alcohol use disorder, now being repurposed for the treatment of metastatic cancers. Developed by researchers at Pirkanmaan hyvinvointialue in Finland, Lipistad is designed to improve the pharmacokinetic profile and stability of disulfiram, which is otherwise rapidly degraded in the bloodstream. The drug's anti-cancer activity is primarily mediated through its metabolite, diethyldithiocarbamate (DDC), which complexes with copper ions to form Cu-DDC. This complex specifically targets and inhibits the NPL4 protein (encoded by the NPLOC4 gene), a critical adaptor for the p97/VCP segregase that is essential for the turnover of polyubiquitinated proteins. Inhibition of the NPL4-p97 pathway leads to proteotoxic stress, accumulation of unfolded proteins, and subsequent apoptosis, particularly in cancer stem cells that overexpress ALDH. Lipistad is currently undergoing Phase 1 clinical evaluation for patients with metastatic breast, ovarian, prostate, and kidney cancers.

Brand names

Lipistad

Other names

liposomal disulfiram