Repaglinide

Protein target name:

ABCC8, KCNJ11

Mechanism of action:

Inhibitor

Recommended Concentration for use in cells:

up to 1 uM

Probe Information

Target and Probe Information

Target Details

Target class:

Ion channel

Subclass:

Potassium channel

HUGO ID:

HGNC:59 HGNC:6257

Entrez gene ID:

6833 3767

UNIPROT ID:

Q09428 Q14654

Target alias:

HI; SUR; HHF1; MRP8; PHHI; SUR1; ABC36; HRINS; TNDM2; SUR1delta2, BIR; HHF2; PHHI; IKATP; TNDM3; KIR6.2; MODY13

Probe Details

Chemical Probes Portal ID:

CPP1806

Probe alias:

Prandin

PubChem CID:

65981

ChEMBL ID:

CHEMBL1272

SMILES string:

CCOc1cc(CC(=O)N[C@@H](CC(C)C)c2ccccc2N3CCCCC3)ccc1C(=O)O

InChi Key:

FAEKWTJYAYMJKF-QHCPKHFHSA-N

Orthogonal probe:

Glyburide

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

IC50

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.

Off target activity

Potency (off target):

IC50

Off target protein and potency:

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).

In cell validation

On target activity in cells

Potency in cells:

IC50

800 nM

Potency assay (cells):

In HEK293 cells, repaglinide inhibited Kir6.2/SUR-1 currents in patch-clamp assay. In islets isolated from Wistar rats, Repaglinide induced insulin release (2.1 ng/islet/hour) at 5 mM glucose.

Target engagement assay (cells):

Yes, patch clamp and competitive binding assays using wild-type (binds repaglinide) and mutant (S1237Y, defective in binding repaglinide) SUR1.

In vivo validation

Organism:

Sprague-Dawley rats

Dose:

1 mg/kg

Route of delivery:

Oral

Organ of Interest

Organ (O):

Pancreas

Target engagement assay:

Indirect; repaglinide decreased blood glucose with an ED50=15.6 ug/kg.

Primary Reference

Reference (doi):

10.2337/diabetes.51.9.2789 10.1016/j.bmcl.2004.07.059 10.2337/diabetes.47.3.345

Reference (PMID):

12196472 15380228 9519738

Under Review

This probe is in the process of SAB review. Please continue to check back for new reviews and commentary.

SAB Rating

Rating for use in Cells

2 review(s)

Rating for use in Model Organisms

2 review(s)

SAB Members

SAB 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.

May 15 2020 - 2:23pm

Repaglinide

Probe Information

Target Details

HI; SUR; HHF1; MRP8; PHHI; SUR1; ABC36; HRINS; TNDM2; SUR1delta2, BIR; HHF2; PHHI; IKATP; TNDM3; KIR6.2; MODY13

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

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Repaglinide

Probe Information

Target Details

HI; SUR; HHF1; MRP8; PHHI; SUR1; ABC36; HRINS; TNDM2; SUR1delta2, BIR; HHF2; PHHI; IKATP; TNDM3; KIR6.2; MODY13

Probe Details

In vitro validation

In cell validation

In vivo validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?