TOIP

TOIP is an AI-designed peptide inhibitor specifically engineered to disrupt the protein-protein interaction (PPI) between TANK-binding kinase 1 (TBK1) and Optineurin (OPTN). Developed using the ProteinMPNN deep learning model based on the crystal structure of the TBK1/OPTN complex (PDB: 5EOF), TOIP is delivered via a selenium nanoparticle system to facilitate intracellular uptake. The drug's mechanism of action involves the suppression of mitophagy and oxidative phosphorylation in acute myeloid leukemia (AML) cells, leading to increased mitochondrial reactive oxygen species (ROS) accumulation and cytotoxicity. Preclinical studies have demonstrated that TOIP reduces leukemic burden and prolongs survival in MOLM13 systemic xenograft and patient-derived xenograft (PDX) models. Furthermore, TOIP has shown the ability to resensitize Venetoclax-resistant AML cells to treatment, suggesting its potential as a translational strategy for refractory leukemia.

Other names

TBK1-OPTN Interaction Inhibitory PeptideTBK-1-OPTN Interaction Inhibitory PeptideTBK 1-OPTN Interaction Inhibitory Peptide