GNS651

GNS651 is a small molecule chloroquine analog and autophagy inhibitor under investigation for its antitumor, anti-inflammatory, and antiviral properties. It acts by inhibiting late-stage autophagy through interaction with palmitoyl-protein thioesterase 1 (PPT1), leading to lysosomal dysfunction, accumulation of unbound zinc ions in lysosomes, impairment of cathepsin activity, blockage of autophagic flux, altered mTOR localization, lysosomal membrane permeabilization, caspase activation, and cell death. GNS651 demonstrates high liver tropism and has shown potent antitumor activity against various human cancer cell lines as well as in vivo models of hepatocellular carcinoma (HCC). It is being developed primarily for advanced liver cancers such as HCC and intrahepatic cholangiocarcinoma (iCCA), including tumors resistant to standard therapies. Clinical trials have also explored its use in patients with advanced or metastatic cancer who have SARS-CoV-2 infection[2][4][5][6][9].