KOTX1 is an inhibitor of aldehyde dehydrogenase 1A3 (ALDH1A3; IC50 = 5.14 nM).1 It potentiates glucose-induced insulin secretion from pancreatic islets isolated from patients with type 2 diabetes when used at a concentration of 10 ?M. KOTX1 (40 mg/kg per day) decreases plasma insulin levels and reduces blood glucose levels in an intraperitoneal glucose tolerance test (IPGTT) in diabetic db/db male mice. It decreases blood glucose levels and increases plasma insulin levels in a mouse model of obesity induced by a high-fat diet when administered in the diet at 270 ppm.
References:
[1]. Son, J., Du, W., Esposito, M., et al.Genetic and pharmacologic inhibition of ALDH1A3 as a treatment of β-cell failureNat. Commun.14(1)558(2023).