KZR-8445, a cyclic depsipeptide, is a client-selective Sec61 inhibitor. KZR-8445 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 inhibits pro-inflammatory cytokine secretion in primary immune cells. KZR-8445 inhibits SARS-CoV-2 replication, virus-induced cytotoxicity, and spike protein biogenesis. KZR-8445 blocks disease progression in a mouse model of rheumatoid arthritis. KZR-8445 can be used for the researches of rheumatoid arthritis and SARS-CoV-2 infection[1].
