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

## TL;DR

This study discovers a new class of marine-derived compounds that activate the STING pathway and show strong anti-tumor effects when combined with a common chemotherapy drug.

## Contribution

A novel series of bromophenol derivatives, including OSBP63, are identified as potent non-CDN STING agonists with anti-tumor activity.

## Key findings

- OSBP63 activates the STING pathway, leading to increased p-IRF3 and IFN-β secretion.
- OSBP63 combined with paclitaxel significantly suppressed BCL-2 and AKT phosphorylation in breast cancer models.
- The compound demonstrates pronounced anti-tumor activity in a mouse model of breast cancer.

## Abstract

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.