Figure 3.

The mechanism of omecamtiv mecarbil. The cardiac myocyte is composed of repeated myofibril units that contain myofilaments. Each unit, termed a sarcomere, is composed of thick and thin filaments, myosin (pink/orange), and actin (purple), respectively. Myosin contains two heads that serve the site of ATPase enzyme that hydrolyzes ATP required for the actin and myosin cross-bridge formation. These heads interact with a binding site on actin and cause the sarcomere length to shorten during contraction. Phosphate is released from ADP to create the force. The more myosin heads containing ADP, the greater the force in each heart contraction. OM binds with highest affinity to myosin heads containing ADP and stabilizes the myosin head in this confirmation 6-fold compared to the other confirmation states. A greater force is produced during each cycle of cardiac contraction. The mechanism has the analogy of hands holding on a rope in which the more hands, the greater the force. ADP = adenosine diphosphate; ATP = adenosine triphosphate; OM = omecamtiv mecarbil.