Open AccessModern methods for the development of new drugs that affect the hemostatic system
Author(s) -
А. В. Сулимов,
Danil Kutov,
Anna Tashchilova,
İvan Ilin,
Н. А. Подоплелова,
М. А. Пантелеев,
И. В. Леденева,
Х. С. Шихалиев,
В. Б. Сулимов
Publication year - 2019
Publication title -
voprosy gematologii/onkologii i immunopatologii v pediatrii
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.108
H-Index - 3
eISSN - 2414-9314
pISSN - 1726-1708
DOI - 10.24287/1726-1708-2019-18-4-136-152
Subject(s) - blood clotting , docking (animal) , fibrin , clotting factor , drug , drug discovery , computational biology , medicine , pharmacology , chemistry , computer science , bioinformatics , intensive care medicine , biology , immunology , biomedical engineering , nursing
The blood coagulation system plays an important role in health and disease. It is a complex network of proteolytic reactions that is activated during injuries and controls the formation of a fibrin clot. Although new components and reactions have not been discovered for thirty years, during this time there has been a revolution in understanding of how this system works and what enzymes are the optimal targets for the therapy. At the same time, new methods of drug development, first of all, computer docking, which are ideally suited for the discovery of inhibitors of blood clotting enzymes, have appeared. In this review, an attempt has been made to correlate the lines of development of new ideas about the mechanisms of coagulation, new methods of searching for drugs and their combination, thanks to which now there are more and more potentially interesting molecules that can change the face of the anticoagulant therapy in the near future. In the review, molecular modeling methods, primarily docking, which are increasingly used at the initial stage of developing new drugs, the role of docking at the initial stage of developing new inhibitors are briefly considered and the structure of the active centers of factors Xa and XIa, which determines their interaction with inhibitors, are discussed in detail.