Repaglinide

Inhibitor of ABCC8, KCNJ11

Structure

SERP Rating

In Cells

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In Model Organisms

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Information

ABCC8
KCNJ11

Inhibitor

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Probe Availability:

In Vitro Validations

Uniprot ID: Q09428

Target Class: Ion Channel

Target SubClass: Potassium channel

Potency: IC50

Potency Value: 106 nM

Potency Assay: In vitro assays with membranes from COS-1 cells expressing SUR-1. A KD of 50 nM was derived from the IC50 value. These data have been replicated in comparable experiments with HEK293 extracts (KD=0.4 nM) and BetaTC3 cells (KD=6.4 nM) using [3H]-labeled repaglinide.

PDB ID for probe-target interaction (3D structure): 6JB3, 6JB1

Target aliases:

ATP-binding cassette sub-family C member 8, SUR1, ...

DOI Reference: 10.2337/diabetes.51.9.2789

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : IC50 SLC22A1: 9,200 nM

Potency assay (off target): Inhibition of 4-(4-(dimethylamino)styryl)-N-methylpyridinium uptake at human OCT1 expressed in HEK293 cells by confocal microscopy (J. Med. Chem., (2008) 51:19:5932)

Probe Selectivity in Vitro:

Inactive against CYP3A4, CYP2C8 and CYP3A5; data from ChEMBL and Probe Miner (http://probeminer.icr.ac.uk/#/Q09428/423).

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

(last updated: 29 Apr 2020 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Repaglinide is a member of the meglitinide family of insulin secretagogues. Like the sulfonylurea class of anti-diabetes drugs, Repaglinide binds and inhibits the KATP (ATP-dependent potassium channel) in beta cells, causing membrane depolarization, calcium influx, and insulin secretion. The meglitinides, however, have slightly different biophysical interactions with the channel, and are more optimized for clinical use than for investigation as a probe in cell culture. If one is studying the KATP channel itself and insulin secretion in cells, the sulfonylureas seem to be quite good probes already, and would be preferable for use in the lab.

(last updated: 15 May 2020 )