REPAGLINIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H36N2O4
Molecular Weight	452.5857
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOC1=C(C=CC(CC(=O)N[C@@H](CC(C)C)C2=C(C=CC=C2)N3CCCCC3)=C1)C(O)=O

InChI

InChIKey=FAEKWTJYAYMJKF-QHCPKHFHSA-N

InChI=1S/C27H36N2O4/c1-4-33-25-17-20(12-13-22(25)27(31)32)18-26(30)28-23(16-19(2)3)21-10-6-7-11-24(21)29-14-8-5-9-15-29/h6-7,10-13,17,19,23H,4-5,8-9,14-16,18H2,1-3H3,(H,28,30)(H,31,32)/t23-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C27H36N2O4
Molecular Weight	452.5857
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020741s040lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12196472

Repaglinide is antidiabetic drug, which is sold under several names including, Prandin in the U.S., Surepost in Japan and GlucoNorm in Canada. It is an oral blood glucose-lowering drug of the meglitinide class used in the management of type 2 diabetes mellitus (also known as non-insulin dependent diabetes mellitus or NIDDM). Repaglinide lowers blood glucose levels by stimulating the release of insulin from the pancreas. This action is dependent upon functioning beta (ß) cells in the pancreatic islets. Insulin secretion by pancreatic β cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Repaglinide closes ATP-dependent potassium channels in the ß-cell membrane by binding at characterizable sites. This potassium channel blockade depolarizes the ß-cell, which leads to an opening of calcium channels. The resulting increased calcium influx induces insulin secretion. The ion channel mechanism is highly tissue selective with low affinity for heart and skeletal muscle. Repaglinide is completely metabolized by oxidative biotransformation and direct conjugation with glucuronic acid after either an IV or oral dose.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sulfonylurea receptor 1 5 Target ID: CHEMBL2071 Sources: https://www.ncbi.nlm.nih.gov/pubmed/?term=12196472	Inhibitor 8228		21.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 256 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020741s040lbl.pdf	Palliative		Approved 8360	PRANDIN Approved Use PRANDIN is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Launch Date 8.8274882E11

C_max

Value	Dose	Co-administered	Analyte	Population
65.8 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020741s040lbl.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:		REPAGLINIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
447.4 ng × h/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020741s040lbl.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:		REPAGLINIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.4 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020741s040lbl.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:		REPAGLINIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020741s040lbl.pdf	4 mg 1 times / day multiple, oral dose: 4 mg route of administration: Oral experiment type: MULTIPLE co-administered:		REPAGLINIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
4 mg 4 times / day multiple, oral Recommended Dose: 4 mg, 4 times / day Route: oral Route: multiple Dose: 4 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020741s041s042lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020741s041s042lbl.pdf Page: p.1	Disc. AE: Hypoglycemia... AEs leading to discontinuation/dose reduction: Hypoglycemia Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020741s041s042lbl.pdf Page: p.1

AEs

AE	Significance	Dose	Population
Hypoglycemia	Disc. AE	4 mg 4 times / day multiple, oral Recommended Dose: 4 mg, 4 times / day Route: oral Route: multiple Dose: 4 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020741s041s042lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020741s041s042lbl.pdf Page: p.1

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-0420	http://www.3bsc.com/index/pro_info.php?id=19776
3B Scientific (Wuhan) Corp	3B1-00402	http://www.3bsc.com/index/pro_info.php?id=20614
AA Blocks	AA00387U	https://www.aablocks.com/goods/Goods/detail?id=AA00387U
AEchem Scientific Corp., USA	AE026283	http://www.aechemsc.com/info_products/AE026283.php
AHH Chemical co.,ltd	API-1401	http://www.ahhchemical.com/product/API-1401.html
AK Scientific, Inc. (AKSCI)	I979	http://www.aksci.com/item_detail.php?cat=I979
Aaron Chemicals	AR0038ZM	http://www.aaronchem.com/135062-02-1
AbMole Bioscience	M3714	http://www.abmole.com/products/repaglinide.html
Achemo Scientific Limited	AC-15094	http://www.achemo.com/search/?Keyword= 135062-02-1
Acorn PharmaTech	ACN-034460	http://www.acornpharmatech.com/
Adooq BioScience	A10783	https://www.adooq.com/repaglinide.html
Alfa Chemistry	AP135062021	https://reagents.alfa-chemistry.com/product/repaglinide-cas-135062-02-1-4126.html
Alsachim	849	http://www.alsachim.com/product-C2672-glo.bal-view.html
Anward	ANW-63956	http://www.anward.com/pro_result/50407
Aurora Fine Chemicals LLC	A12.866.669	http://online.aurorafinechemicals.com/info?ID=A12.866.669
Aurum Pharmatech LLC	W-5210	http://www.Aurumpharmatech.com/Product/ProductDetails/W_5210
AvaChem Scientific	2452	http://www.avachem.com/productSearch.asp?2452
Axon MedChem	3365	https://www.axonmedchem.com/product/3365
BLD Pharm	BD145505	http://www.bldpharm.com/products/135062-02-1.html
BioChemPartner	BCP04250	http://www.biochempartner.com/135062-02-1-BCP04250
BioCrick	BCC2504	http://www.biocrick.com/Repaglinide-BCC2504.html
BioSynth	Q-201663	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-201663.html
Boerchem	BC220160	http://www.boerchem.com/?product_37161.html
CSNpharm	CSN11584	https://www.csnpharm.com/products/repaglinide.html
Chem Scene	CS-0979	http://www.chemscene.com/135062-02-1.html
ChemMol	2100020	http://www.chemmol.com/chemmol/2100020.html
ChemMol	30108903	http://www.chemmol.com/chemmol/30108903.html
ChemMol	44006201	http://www.chemmol.com/chemmol/44006201.html
ChemMol	49409344	http://www.chemmol.com/chemmol/49409344.html
ChemMol	97900803	http://www.chemmol.com/chemmol/97900803.html
Chemenu	CM110380	http://www.chemenu.com/products/CM110380
Chemspace	CSSB00000051725	https://chem-space.com/CSSB00000051725
DC Chemicals	DCAPI1444	http://www.dcchemicals.com//product_show-Repaglinide.html
Enamine	Z1777729210	https://www.enaminestore.com/catalog/Z1777729210
Glentham Life Sciences	GP2014	http://www.glentham.com/products/product/GP2014/
Hello Bio	HB1106	https://www.hellobio.com/repaglinide.html
LGC Standards	DRE-C16809400	https://www.lgcstandards.com/US/en/p/DRE-C16809400
LGC Standards	LGCFOR0944.00	https://www.lgcstandards.com/US/en/p/LGCFOR0944.00
LGC Standards	MM0944.00-0250	https://www.lgcstandards.com/US/en/p/MM0944.00-0250
Lab Network	LN00337273	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00337273
MedChem Express	HY-15209	https://www.medchemexpress.com/Repaglinide.html
OChem	5053	http://www.ocheminc.com/index.php?act=psearch&pid=62R021
Selleck Chemicals	S1426	http://www.selleckchem.com/products/Repaglinide.html
Sigma-Aldrich	Y0000457_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/y0000457?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	Y0000458_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/y0000458?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	R9028_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/r9028?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1600813_USP	https://www.sigmaaldrich.com/catalog/product/usp/1600813?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S517523	http://www.smolecule.com/products/s517523
Smolecule	S541214	http://www.smolecule.com/products/s541214
TCI (Tokyo Chemical Industry)	R0179	http://www.tcichemicals.com/eshop/en/us/commodity/R0179/index.html
THE BioTek	bt-258096	https://www.thebiotek.com/product/inhibitors/bt-258096
THE BioTek	bt-280064	https://www.thebiotek.com/product/inhibitors/bt-280064
Tocris	3805	https://www.tocris.com/products/repaglinide_3805
VladaChem	VL263901-1g	https://www.vladachem.com/product.php?products=135062-02-1
Yuhao Chemical	RT6545	http://www.chemyuhao.com/135062-02-1.html
abcr GmbH	AB436463	http://www.abcr.com/shop/en/AB436463
eNovation Chemicals	D320161	http://www.enovationchem.com/productDetails.asp?productID=D320161
eNovation Chemicals	D915089	https://www.enovationchem.com/ProductDetails.asp?ProductID=D915089
iChemical	EBD39218	http://www.ichemical.com/chemicals/cas-135062-02-1
mcule	MCULE-3611790330	https://mcule.com/MCULE-3611790330/

PubMed

Title	Date	PubMed
Effectiveness of nateglinide on in vitro insulin secretion from rat pancreatic islets desensitized to sulfonylureas.	2001	12369729
Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers.	2001	11460577
Repaglinide and diabetes: new preparation. No better than glucose-lowering sulphonamides.	2001 Feb	11503861
Combination therapy in type 2 diabetes: the role of repaglinide.	2001 Jan 25	11235608
Current understanding regarding the role of repaglinide in post-prandial hyperglycemia.	2001 Jan 25	11235606
Effect of repaglinide on cloned beta cell, cardiac and smooth muscle types of ATP-sensitive potassium channels.	2001 Jun	11440368
[Large general practice study with repaglinide. Fewer "anxiety eating" in diabetic patients].	2001 Mar 8	11277117
Repaglinide improves blood glucose control in sulphonylurea-naive type 2 diabetes.	2001 Sep	11483229
Rapid acting insulinotropic agents: restoration of early insulin secretion as a physiologic approach to improve glucose control.	2001 Sep	11472274
Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection.	2002	12405866
Study of the insulinotropic effect of the novel antihyperglycemic agent KAD-1229 using HIT T15 cells, a hamster's insulinoma cell line.	2002	12236048
Control of post-prandial hyperglycemia--an essential part of good diabetes treatment and prevention of cardiovascular complications.	2002 Apr	12189909
A novel simple method for the investigation of drug binding to the K(ATP) channel sulfonylurea receptor.	2002 Aug 15	12202259
Sulfonylurea stimulation of insulin secretion.	2002 Dec	12475777
No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers.	2002 Dec	12463731
Oral antihyperglycemic therapy for type 2 diabetes: scientific review.	2002 Jan 16	11790216
Preventing the progressive nature of type 2 diabetes.	2002 Jul-Aug	12402899
Current oral agents for type 2 diabetes. Many options, but which to choose when?	2002 May	12040862
[Glinides and glitazones in diabetes treatment. Are they really effective?].	2002 May 2	12422705
Hypoglycemia probably due to accidental intake of repaglinide.	2002 Nov	12553369
[Repaglinide (NN-623)].	2002 Sep	12387050
[Structures and mechanisms for non SU insulin secretagogues].	2002 Sep	12387019
Differential interactions of nateglinide and repaglinide on the human beta-cell sulphonylurea receptor 1.	2002 Sep	12196472
Type 2 diabetes management: a comprehensive clinical review of oral medications.	2002 Spring	11894443
Economic model of first-line drug strategies to achieve recommended glycaemic control in newly diagnosed type 2 diabetes mellitus.	2003	12859222
Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one-year, randomized, double-blind assessment of metabolic parameters and cardiovascular risk factors.	2003 Feb	12749508
Pharmacokinetics of repaglinide in healthy caucasian and Japanese subjects.	2003 Jan	12520624
The effect of repaglinide on insulin secretion and oxidative stress in type 2 diabetic patients.	2003 Jan	12482641
A comparison of costs for four oral antidiabetic regimens within a managed care population.	2003 Jul	12908215
[symbol: see text] Nateglinide and [symbol: see text] repaglinide for type 2 diabetes?	2003 Jul	12879789
[Meglitinide analogs: new insulinotropic agents for the treatment of non-insulin dependent diabetes].	2003 Jun	12891883
Influence of drugs interacting with CYP3A4 on the pharmacokinetics, pharmacodynamics, and safety of the prandial glucose regulator repaglinide.	2003 Jun	12817528
Comparison of glycaemic control and cardiovascular risk profile in patients with type 2 diabetes during treatment with either repaglinide or metformin.	2003 Jun	12757988
Metformin-induced hemolytic anemia in a patient with glucose-6- phosphate dehydrogenase deficiency.	2003 Mar	12610074
Safety and efficacy of repaglinide in type 2 diabetic patients with and without impaired renal function.	2003 Mar	12610054
Differential selectivity of insulin secretagogues: mechanisms, clinical implications, and drug interactions.	2003 Mar-Apr	12623163
Neuronal calcium sensor proteins are direct targets of the insulinotropic agent repaglinide.	2003 Oct 1	12844348
Cardiovascular risk in type 2 diabetics and pharmacological regulation of mealtime glucose excursions.	2003 Sep	14526261
Lack of effect of acute repaglinide administration on postprandial lipaemia in patients with type 2 diabetes mellitus.	2003 Sep	14520605
CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide.	2003 Sep	12919179

Patents

Sample Use Guides

In Vivo Use Guide

There is no fixed dosage regimen for the management of type 2 diabetes with PRANDIN (repaglinide). PRANDIN doses are usually taken within 15 minutes of the meal but time may vary from immediately preceding the meal to as long as 30 minutes before the meal. For patients not previously treated or whose HbA1c is < 8%, the starting dose should be 0.5 mg with each meal. For patients previously treated with blood glucose-lowering drugs and whose HbA1c is > 8%, the initial dose is 1 or 2 mg with each meal preprandially.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:21:09 UTC 2023` Edited by `admin` on `Wed Jul 05 23:21:09 UTC 2023`
Record UNII	668Z8C33LU
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

REPAGLINIDE

Official Name

English

REPAGLINIDE [EP MONOGRAPH]

Common Name

English

NSC-759893

Code

English

PRANDIN

Brand Name

English

REPAGLINIDE [MART.]

Common Name

English

REPAGLINIDE [VANDF]

Common Name

English

Repaglinide [WHO-DD]

Common Name

English

A10BX02

Code

English

REPAGLINIDE [USAN]

Common Name

English

AGEE-623ZW

Code

English

REPAGLINIDE [USP-RS]

Common Name

English

REPAGLINIDE [ORANGE BOOK]

Common Name

English

REPAGLINIDE [JAN]

Common Name

English

REPAGLINIDE [MI]

Common Name

English

(+)-2-ETHOXY-.ALPHA.-(((S)-.ALPHA.-ISOBUTYL-O-PIPERIDINOBENZYL)CARBAMOYL)-P-TOLUIC ACID

Common Name

English

REPAGLINIDE [USP MONOGRAPH]

Common Name

English

AG-EE 623 ZW

Code

English

AG-EE-623-ZW

Code

English

AG-EE-623ZW

Code

English

REPAGLINIDE [EMA EPAR]

Common Name

English

repaglinide [INN]

Common Name

English

(S)-2-ETHOXY-4-(2-(METHYL-1-(2-(1-PIPERIDINYL)PHENYL)BUTYLAMINO)-2-OXOETHYL)-BENZOIC ACID

Systematic Name

English

Classification Tree Code System Code

WHO-VATC

QA10BD14