Development of a lasmiditan analogue for treatment of acute kidney injury

DESCRIPTION (provided by applicant): The long-term goal of this project is to develop a safe and efficacious therapeutic small molecule for treatment of acute kidney injury (AKI). AKI results from diverse insults such as sepsis, ischemia-reperfusion (I/R)or nephrotoxicant exposure and nearly half of those who develop AKI do not survive. Since treatment remains largely palliative and survival rates have remained unchanged for several decades, new therapeutic approaches are desperately needed. The role of mitochondrial dysfunction in animal models of AKI has been validated, but there is no approved therapeutic that specifically targets mitochondrial biogenesis (MB) to stimulate mitochondrial function and restore renal function. We have recently published a proof-of-principle study using the ?2-adendergic receptor agonist formoterol that demonstrates stimulation of MB restores mitochondrial function and accelerates recovery from AKI in a murine model (Jesinkey et al., JASN-2013-09-0952). Lasmiditan, a 5-HT