Marine Bromophenol Derivatives as a Novel Class of Potent Small-Molecule STING Agonists

Activation of the stimulator of interferon genes (STING) pathway has emerged as a promising strategy for Cancer Immunotherapy. However, the initial cyclic dinucleotide (CDN) analogs developed as STING agonists have shown limited efficacy in clinical trials, prompting interest in non-CDN small-molecule alternatives. In this study, we identified a novel series of bromophenol derivatives as effective STING agonists. Among these derivatives, OSBP63 robustly activated the STING signaling pathway, resulting in enhanced phosphorylation of interferon regulatory factor 3 (p-IRF3) and increased secretion of interferon-β (IFN-β). Co-administration of Marine Bromophenol Derivative (OSBP63) with paclitaxel (PTX), a conventional Anticancer drug, significantly suppressed B-cell lymphoma-2 (Bcl-2) expression and protein kinase B (Akt) phosphorylation, thereby demonstrating pronounced anti-tumor activity in a mouse model of Breast Cancer. These findings suggest that OSBP63 represents a promising non-CDN small-molecule STING agonist candidate, offering a valuable lead for future Anticancer therapeutic development.