Investigation of the tight binding mechanism of a new anticoagulant DD217 to factor Xa by means of molecular docking and molecular dynamics.

A new promising drug candidate DD217 has been proposed recently as a potent anticoagulant acting on factor Xa (fXa) target. It exhibits the lowest concentration of doubling the prothrombin time among the known anticoagulants. In order to explain the efficacy of DD217 in terms of molecular interactions with its target we studied the hypothesis of the tight binding mechanism by means of molecular dynamics simulations and statistical analysis of the trajectory.

The Development of New Low-Molecular-Weight Factor Xa Inhibitors that are Potential Anticoagulants.

Background: Despite the introduction of direct oral anticoagulants, the search for new oral anticoagulants remains an urgent task.

Objective: By using docking and scoring, based on physical methods, simple chemical rules, methods of synthesis, and activity measurement, develop new low-molecular-weight inhibitors of factor Xa, which are potential anticoagulants.

Methods: The development of leads was based on chemical synthesis and structure-based drug design methods.

The Development of New Factor Xa Inhibitors Based on Amide Synthesis.

Background: Factor Xa (FXa) is known to play a central role in blood coagulation cascade and considered to be one of the most attractive targets for oral anticoagulants of new generation.

Objective: Our approach for the development of directly acting oral anticoagulants (DOAC), FXa inhibitors was demonstrated in this work.

Method: Chemical synthesis is the base of our approach for the development of potential inhibitors.