# Discovery of a novel RSK2 inhibitor for the treatment of metastatic pancreatic cancer

## TL;DR

This study discovers a new RSK2 inhibitor, NSYSU-115, which shows promise in treating metastatic pancreatic cancer by reducing cell growth and migration.

## Contribution

The novel RSK2 inhibitor NSYSU-115 was identified and shown to suppress pancreatic cancer cell viability and migration.

## Key findings

- NSYSU-115 inhibited RSK2 with an IC50 of 45.5 nM and suppressed colony formation and cell viability.
- The inhibitor reduced phosphorylation of IκBα and impaired cell migration and EMT markers.
- NSYSU-115 shows therapeutic potential for metastatic pancreatic cancer treatment.

## Abstract

Pancreatic cancer is among the most lethal malignancies, with a five-year survival rate of only 6%. For patients with metastatic disease, current treatments extend median survival by merely four months. This study addresses the urgent need for targeted therapies, as no specific drugs are currently available. Clinical analyses revealed significantly elevated RSK2 expression in pancreatic cancer tissues, associated with shorter survival. We aimed to identify a novel RSK2 inhibitor for metastatic pancreatic cancer. Through structure-based virtual screening, we identified NSYSU-115 as a promising candidate with an IC50 of 45.5 nM. At low concentrations, NSYSU-115 significantly suppressed colony formation, while higher concentrations reduced cell viability and proliferation. It also inhibited phosphorylation of IκBα, a known RSK2 substrate, in a dose- and time-dependent manner. Furthermore, NSYSU-115 impaired cell migration and altered epithelial-mesenchymal transition (EMT) markers. These findings highlight NSYSU-115 as a potent kinase inhibitor with promising therapeutic potential for pancreatic cancer treatment.