| Description |
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].
|
| Related Catalog |
|
| 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]. Animal Model: Male C57BL/6 mice (10–12 weeks age) Dosage: 50 mg/kg (Pharmacokinetic analysis) Administration: I.p.; 4 hours Result: led to a significant increase in blood glucose at 60 minutes.
|
| References |
[1]. Kharade SV, et al. Structure-Activity Relationships, Pharmacokinetics, and Pharmacodynamics of the Kir6.2/SUR1-Specific Channel Opener VU0071063. J Pharmacol Exp Ther. 2019;370(3):350-359. [2]. Raphemot R, et al. Direct activation of β-cell KATP channels with a novel xanthine derivative. Mol Pharmacol. 2014;85(6):858-865.
|
