Virtual screening and ADMET analysis in identification of new human 17,20-lyase (CYP17A1) inhibitors

The article describes the development of a robust pharmacophore model and pharmacophore screening of poten tial inhibitors of the 17,20-lyase activity of the human CYP17A1 enzyme – an important target in the treatment of prostate cancer. To choose the compounds with the best pharmacokinetics parameters ADMET analysis was performed. According to the calculated data of flexible molecular docking, there were found five compounds with low free energies of binding to the catalytic center of the enzyme, which are comparable to the experimental value of the CYP17A1 inhibitor abiraterone used in clinical practice for treatment castration-resistant prostate cancer. It was established that the connection of the identified compounds with the enzyme is due to van der Waals, lipophilic, electrostatic and intermolecular hydrogen bonds with amino acid residues of the active center and π-stacking with the heme group of the enzyme. The results obtained will be used to develop new drugs with minor side effects for the treatment of prostate cancer due to inhibition of the 17,20-lyase activity of CYP17A1.