TH-Z145

TH-Z145 may be used as a research tool in studies investigating the mevalonate pathway and its implications in various biological processes, including cancer and inflammation. It may also be used as a potent vaccine adjuvant to enhance immune responses by targeting the mevalonate pathway to improve the efficacy of vaccines.

Potent and selective mevalonate (MVA) pathway geranylgeranyl diphosphate synthase (GGPPS) inhibitor that stimulates immune responses in vivo.

TH-Z145 is a potent and selective geranylgeranyl diphosphate synthase (GGPPS) inhibitor (IC50 = 210 nM; FPPS IC50 > 30 µM) that stimulates immune responses by blocking the mevalonate (MVA) pathway-mediated post-translational protein geranylgeranylation. When co-administered with antigen in mice in vivo, TH-Z145 triggers strong adjuvant responses, increasing OVA-specific antibody titres (in mice immunized with 100 μg OVA + 100 μg TH-Z145) and protecting against death caused by live influenza virus PR8 challenge (in mice immunized with 5 μg PR8 HA1 subunit containing TH-Z145). TH-Z145 adjuvant efficacy is blocked by GGPP and synergized with HMG-CoA inhibitor simvastatin.