KZR-8445 TFA, a cyclic depsipeptide, is a client-selective Sec61 inhibitor. KZR-8445 TFA binds to the fully opened Sec61 lateral gate, blocks lumenal plug domain access, stabilizes lateral gate helices, traps select signal peptides, and disrupts secretory and membrane protein biogenesis. KZR-8445 TFA inhibits pro-inflammatory cytokine secretion in primary immune cells. KZR-8445 TFA inhibits SARS-CoV-2 replication, virus-induced cytotoxicity, and spike protein biogenesis. KZR-8445 TFA blocks disease progression in a mouse model of rheumatoid arthritis. KZR-8445 TFA can be used for the researches of rheumatoid arthritis and SARS-CoV-2 infection[1].
