TY - JOUR T1 - Inhibition of Peroxidase Activity of Cytochrome <em>c: De Novo</em> Compound Discovery and Validation JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.115.097816 SP - mol.115.097816 AU - Ahmet Bakan AU - Alexandr A. Kapralov AU - Hulya Bayir AU - Feizhou Hu AU - Valerian E. Kagan AU - Ivet Bahar Y1 - 2015/06/15 UR - http://molpharm.aspetjournals.org/content/early/2015/06/15/mol.115.097816.abstract N2 - Cytochrome c (cyt c) release from the mitochondria is accepted to be the point of no return for eliciting a cascade of interactions that lead to apoptosis. A strategy for containing sustained apoptosis is to reduce the mitochondrial permeability pore opening. The latter is enhanced by peroxidase activity of cyt c gained upon its complexation with cardiolipin in the presence of reactive oxygen species. Blocking access to the heme group has been proposed as an effective intervention method for reducing, if not eliminating the peroxidase activity of cyt c. In the present study, using a combination of druggability simulations, pharmacophore modeling, virtual screening and in vitro fluorescence measurements to probe peroxidase activity, we identified three repurposable drugs and seven compounds that are validated to effectively inhibit the peroxidase activity of cyt c. ER -