3.1 Introduction and discovery
The discovery of Omecamtiv mecarbil (OM) was by chance, in 1988 a group of scientists were screening for compounds that could be developed as novel antimitotic therapy for the treatment of cancer. However they observed that a number of compounds were activating rather than inhibiting the activity of a microtubule based motor protein. This observation raised the point that increasing the activity of a motor protein, namely myosin could have therapeutic benefits in the setting of systolic HF (Malik and Morgan, 2011).
Current drugs designed for the treatment of systolic HF act to block the neurohumoral response by inhibition of the RASS, adrenergic block and aldosterone antagonism, however non are focused on improving the contractile function of the heart (McMurray, 2010). In theory improving the contractile function of the heart would reduce the neurohumoral activation and improve or stabilise the decline in cardiac function. Previous attempts to increase cardiac function by using inotropes, such as β-adrenergic receptor agonists and phosphodiesterase inhibitors, which work by activating secondary messenger pathways that increase intracellular calcium, have been unsuccessful. In clinical trials they have resulted in arrhythmias, increased heart rate and oxygen consumption and have increased mortality (Cohn et al., 1998; Cuffe et al., 2002; Packer et al., 1991; Petersen and Felker, 2008).
Due to the adverse effects caused by drugs that act