In our latest study, we designed and evaluated a new series of thioxo–tetrahydro–pyrimidine–benzenesulfonamide compounds (P01–P16), inspired by second-generation BRAF inhibitors.

What we did:

• Used molecular docking and molecular dynamics simulations (powered by HPC infrastructure) to predict binding to the BRAFV600E protein

• Conducted biological assays to test anti-proliferative activity across multiple cancer cell lines

• Evaluated kinase inhibition performance against BRAFV600E

Key findings:

• Compounds P09 (MCF-7), P13 (HePG2, TPC-1), and P02 (A375) demonstrated strong anti-proliferative effects

• P14 showed the highest BRAFV600E kinase inhibition, outperforming the reference drug sorafenib

• SAR analysis suggests electron-withdrawing substituents improve both cellular and enzyme inhibitory activity

This research is another step toward computationally guided cancer drug discovery, highlighting how HPC accelerates the path from molecular design → biological testing → potential therapeutic leads.

Read the paper: https://doi.org/10.1016/j.molstruc.2025.143620

Title: Thioxo-tetrahydro-pyrimidin-benzenesulfonamide hybrids as potential BRAFV600E inhibitors: experimental, computational and biological evaluations

Research supported by the Croatian Science Foundation (IP-2022-4658) and powered by the Supek supercomputer at SRCE, University of Zagreb.