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Human STING-specific macrocyclic peptide Nano-P1 displays limited toxicity to MEFs and potently suppresses cGAS-STING activation

ABSTRACT: Suppression of hyperactive STING may provide therapeutic benefits to treat inflammatory diseases. We identified a macrocyclic peptide, named P1, which binds to human STING (hSTING) by a new platform for the discovery of pseudo-natural macrocyclic peptides. Nano-P1, the nanoparticle form to increase P1 cellular membrane permeability, inhibited the 2'3'-cGAMP induced hSTING activation in Mouse Embryonic Fibroblasts (MEFs). In cellular experiments, Nano-P1 effectively blocked the translocation of hSTING from endoplasmic reticulum (ER) to the trans-Golgi network, increasing the accumulation of hSTING on ER, and thus interrupted the downstream STING signaling transduction, which resulted in reduced production of IFN-β and pro-inflammatory cytokines, the major effectors of STING pathway. Furthermore, in vitro data showed a limited toxicity of Nano-P1 toward MEFs, preliminarily supporting its safety profile in most cell types. Overall, Nano-P1 emerges as a safe and potent hSTING inhibitor for potential application in clinical diseases associated with aberrant cGAS-STING activation.

ORGANISM(S): Mus musculus

PROVIDER: GSE309742 | GEO | 2026/09/10

REPOSITORIES: GEO

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Human STING-specific macrocyclic peptide Nano-P1 displays limited toxicity to MEFs and potently suppresses cGAS-STING activation

Project description:Human STING-specific macrocyclic peptide Nano-P1 displays limited toxicity to MEFs and potently suppresses cGAS-STING activation

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