This figure depicts the "cyclic nucleotide" signaling pathways. Activation of these pathways leads to relaxation of smooth muscles. Many drugs work on cell surface receptors to activate cellular signaling pathways, such as β-agonists (Serevent) and peptides (Natrecor). Other drugs work inside the cell and modify signaling events, such as nitric oxide donors (NicOx) and phosphodiesterase inhibitors (Pletal and Viagra). These signaling pathways converge by activating a protein called heat shock related protein 20 (HSP20). AZX-100 is a cell permeant peptide that mimics HSP20 and bypasses the signaling pathways leading to smooth muscle relaxation. This mechanism of action is particularly important in certain patients, such as the one in six asthmatics that has a mutation in the β-receptor (β16 Arg/Arg genotype) or in some forms of vasospasm (such as subarachnoid hemorrhage induced vasospasm which leads to strokes). In these patients, currently available drugs are ineffective and in some cases even harmful.
