TY - JOUR T1 - Inhibition of Peroxidase Activity of Cytochrome <em>c</em>: De Novo Compound Discovery and Validation JF - Molecular Pharmacology JO - Mol Pharmacol SP - 421 LP - 427 DO - 10.1124/mol.115.097816 VL - 88 IS - 3 AU - Ahmet Bakan AU - Alexandr A. Kapralov AU - Hulya Bayir AU - Feizhou Hu AU - Valerian E. Kagan AU - Ivet Bahar Y1 - 2015/09/01 UR - http://molpharm.aspetjournals.org/content/88/3/421.abstract N2 - Cytochrome c (cyt c) release from 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. Pore opening 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 -