Open AccessDiscovery of GPX4 inhibitor by molecular docking simulation as a potential ferroptosis inducer
Author(s) -
Ani Fatonah,
Usman Sumo Friend Tambunan,
Wilis Okti Pamungkas,
Gana Lahirin Dewanto,
Ig. Satrio Wicaksono
Publication year - 2020
Publication title -
biointerface research in applied chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.216
H-Index - 11
ISSN - 2069-5837
DOI - 10.33263/briac101.929933
Subject(s) - gpx4 , lipinski's rule of five , programmed cell death , docking (animal) , inducer , chemistry , cancer cell , biochemistry , computational biology , enzyme , glutathione , cancer , apoptosis , biology , glutathione peroxidase , gene , medicine , genetics , nursing , in silico
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.