From Idea to Drug Candidate: What Happens When Chemistry and HPC Work Together

Published paper in "Journal of Molecular Structure": "Thioxo-tetrahydro-pyrimidin-benzenesulfonamide hybrids as potential BRAFV600E inhibitors: experimental, computational and biological evaluations"

Nov 6th 2025

From Idea to Drug Candidate: What Happens When Chemistry and HPC Work Together

New Research Published!

HPC-Driven Discovery of Potential BRAFV600E Inhibitors in Cancer Treatment

The BRAFV600E mutation is a major oncogenic driver found in melanoma, thyroid cancer, colorectal cancer, and several other malignancies — representing ~90% of all BRAF mutations.

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.

Scientific Paper

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

Search Ruđer Bošković Institute

From Idea to Drug Candidate: What Happens When Chemistry and HPC Work Together

Scientific Paper

Institut Ruđer Bošković

Phone:

+385 1 4561 111

From Idea to Drug Candidate: What Happens When Chemistry and HPC Work Together

Scientific Paper

Related News

CIR Computer Science Seminar: Distributed CholeskyQR for ill-conditioned matrices

EUROCC2 Newsletter - June 2024

EUROCC2 Newsletter - April 2024

EUROCC2 Newsletter - April 2025

High Performance Computing Essential for Economic Development