# Identification of a New Interesting BAG3 Modulator Able to Disrupt Cancer‐Related Pathways

## TL;DR

Researchers identified a new compound that targets BAG3, a protein involved in cancer pathways, showing promise as a potential anticancer drug.

## Contribution

The study introduces a novel BAG3 modulator (compound 2) with strong binding and cytotoxic activity, offering a new direction for anticancer drug development.

## Key findings

- Compound 2 shows tight interaction with BAG3 and significant cytotoxic activity.
- It induces apoptosis in HeLa cells, as shown by Annexin V/PI staining.
- The triazole scaffold is highlighted as a promising platform for future drug development.

## Abstract

Continuing the research aimed at discovering new BAG3 modulators as attractive anticancer drug candidates, a screening campaign on an in‐house library is performed, including compounds featuring a large variety of scaffolds. The obtained results prompted a focus on the triazole moiety and, following a stepwise structural refinement of this scaffold guided by biophysical assays and computational studies, a very attractive compound (2) is identified showing a tight interaction with BAG3 and displaying a significant cytotoxic activity. The discovery of compound 2, whose effects on apoptosis and proteostasis confirm the disruption of BAG3‐related pathways, is particularly relevant given the limited number of BAG3 modulators reported so far. Moreover, the computational data highlight the potential to further explore the triazole scaffold for the development of more potent anticancer agents.

Compound 2, identified through in‐house screening and derived from SP18, exhibits high affinity for BAG3, as demonstrated by Surface Plasmon Resonance and docking studies. It induces a dose‐dependent proapoptotic response in HeLa cells, evidenced by increased Annexin V/PI staining, underscoring the triazole scaffold as a promising platform for BAG3‐targeted anticancer drug development.© 2025 WILEY‐VCH GmbH