Discovery of GPX4 inhibitor by molecular docking simulation as a potential ferroptosis inducer

Ani Fatonah 1, Usman Sumo Friend Tambunan 1,*, Wilis Okti Pamungkas 1, Gana Lahirin Dewanto 1, Ig Satrio Wicaksono 1

1Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, 16424, Depok, Indonesia

*corresponding author e-mail address:  | Scopus ID 56288932400

Biointerface Research in Applied Chemistry, Volume 10, Issue 1, 2020, 4929 – 4933,


As one of the most complex diseases in the world, cancer continues as one of the significant public health problems. It was recorded by 2014 that cancer caused 1,551,000 death in Indonesia. One type of programmed cell death (PCD) that played a role in cancer cell treatment is Ferroptosis. Ferroptosis is PCD on iron and characterized by the inactivation of glutathione-dependent peroxidase (GPx4). In this research, a new therapeutic strategy for cancer was developed through the computational approach on synthetic compounds to discover its potential as an inhibitor of GPx4. About 688 compounds derivative from mercaptosuccinic acid acquired from the Zinc15 database. These compounds screened through the Lipinski’s Rule of Three and pharmacological prediction to eliminate ligands with undesired molecular properties. After that, the ligands underwent both rigid and flexible molecular docking simulations to predict their inhibition activity toward GPx4. From molecular docking simulation, (2S)-2-[(Z)-3-phenylprop-2-enyl]sulfanylbutanedioic acid show favorable characteristics as a drug candidate.

Keywords: Cancer; Ferroptosis; GPx4; Mercaptosuccinic Acid; Molecular Docking Simulation.