0123-A1

0123-A1 is a synthetic blocking peptide designed to disrupt the interaction between the mitochondrial protein ATAD3A and Voltage-Dependent Anion Channel 1 (VDAC1). In lung adenocarcinoma (LUAD), ATAD3A binds to the 100-200 amino acid region of VDAC1, inhibiting its oligomerization and preventing the release of mitochondrial DNA (mtDNA) into the cytosol. This inhibition impairs the cGAS-STING pathway and subsequent anti-tumor immune responses. By disrupting the ATAD3A-VDAC1 complex, 0123-A1 promotes mtDNA release, leading to the infiltration of phagocytic CD274+ macrophages and the activation of CD8+ T cells. Preclinical studies have shown that 0123-A1 enhances the efficacy of immune checkpoint inhibitors (ICIs) in LUAD models, suggesting its potential as a combination strategy for immunotherapy.