That all derivatives displayed lower potency than their parent inhibitor TG (IC50 = 56 nM) can be explained by their more complex, slower binding mode (which requires accommodation of the incorporated azobenzene group). Given the relatively short duration of the activity assays -1.5 hours total exposure time to inhibitors -the compounds may have lacked sufficient time to fully bind the protein, as observed for other TG derivatives. However, longer time scales also obscure cis/trans purity and the experiments are deemed sufficient for initially evaluating AzTG derivative performance, and both AzTG-4 and AzTG-6 demonstrate potency. A critical finding from these experiments is that the relative potency of the cis-and trans-configurations of each compound was influenced by linker length. Both trans-AzTG-2 and trans-AzTG-4 exhibited a reduced IC50 compared to their ciscounterpart. Remarkably, the specificity profile for AzTG-6 was reversed, where cis-AzTG-6 showed a more potent inhibition of SERCA than trans-AzTG-6. This is significant as therapeutic use would ideally require the thermodynamically-stable (transconfiguration) state to be inert, with a biological response elicited only upon highly-localised switching to a more potent, lightdependent (cis-configuration) state.