VU0071063

VU0071063 is a potent and specific Kir6.2/SUR1 opener (EC₅₀=7.44 μM) and can be used for investigating Kir6.2/SUR1 expressed in the pancreas and brain. VU0071063 inhibits insulin secretion by inducing hyperpolarization of β-cell membrane potential. VU0071063 chemotype has a very steep structure-activity relationships^[1][2]. IC50 & Target: EC50: 7.44 μM (Kir6.2/SUR1)^[1] In Vitro: VU0071063 (1 nM~1 mM; HEK-293 cells) dose dependently opens Kir6.2/SUR1. VU0071063 (0~20 μM; isolated cells) inhibits β-Cell excitability in mouse Islets. VU0071063 (10 μM; 1 hour; isolated cells) inhibits glucose-stimulated insulin secretion^[1].
VU0071063 dose dependently and reversibly hyperpolarizes the β-cell membrane potential, which, in turn, inhibits glucose-stimulated Ca²⁺ entry and insulin secretion. The actions of VU0071063 on the β-cell membrane potential are reversed by tolbutamide, and glucose stimulated insulin secretion is unaffected by the inactive analog 34MT, indicating that the effects are mediated through Kir6.2/SUR1^[1]. In Vivo: VU0071063 (50 mg/kg; i.p.; 4 hours) leads to a significant increase in blood glucose at 60 minutes^[1].