Sec61 Inhibitor

Sec61-IN-1 (compound A317) is a potent sec61 inhibitor that effectively targets glioma cells and enhances T cell cytotoxic effects[1][2].

Sec61-IN-3 is a Sec61 inhibitor. Sec61-IN-3 shows a significant inhibitory effect on PD-1 related reporter gene cell models (PD1tsGluc) (IC₅₀ = 42 nM), and also has certain inhibitory activity on Her3 (IC₅₀ = 99 nM), IL2 (IC₅₀ = 144 nM) related reporter pathways, but has a relatively weak inhibitory effect on the TNFα (IC₅₀ = 580 nM) pathway. Sec61-IN-3 can be used for cancer research.

Sec61-IN-2 is a Sec61 inhibitor. Sec61-IN-2 shows a significant inhibitory effect on PD-1 related reporter gene cell models (PD1tsGluc) (IC₅₀ = 42 nM), while it has almost no inhibitory activity in TNFα, Her3, and IL-2 pathway models. Sec61-IN-2 can be used for cancer research.

KZR-261 is a Sec61 translocase inhibitor. KZR-261 binds directly to the Sec61 channel, thereby inhibiting the biosynthesis of certain Sec61 substrate proteins, including oncogenic factors. KZR-261 activates the endoplasmic reticulum stress response. KZR-261 exhibits broad in vitro anticancer activity. KZR-261 shows antitumor efficacy in mouse models of cancer. KZR-261 can be used for the research of multiple myeloma, colorectal cancer, small cell lung cancer, pancreatic cancer, prostate cancer, non-Hodgkin's lymphoma, and mantle cell lymphoma.

VGD020 is a highly potent and selective Sec61 translocon inhibitor. VGD020 suppresses the expression of cell surface CD4 by inhibiting signal peptide-dependent co-translational ER translocation, interferes with the initiation of ER translocation of dengue virus polyprotein, and reduces the expression of Sortilin in breast cancer cells. VGD020 exhibits broad anti-flavivirus and anti-HIV activities. VGD020 can be used in research related to dengue virus infection, Zika virus infection, yellow fever virus infection, human immunodeficiency virus infection, and breast cancer.

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.

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.