GLIMEPIRIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H34N4O5S
Molecular Weight	490.616
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CCC1=C(C)CN(C(=O)NCCC2=CC=C(C=C2)S(=O)(=O)NC(=O)N[C@H]3CC[C@H](C)CC3)C1=O

InChI

InChIKey=WIGIZIANZCJQQY-RUCARUNLSA-N

InChI=1S/C24H34N4O5S/c1-4-21-17(3)15-28(22(21)29)24(31)25-14-13-18-7-11-20(12-8-18)34(32,33)27-23(30)26-19-9-5-16(2)6-10-19/h7-8,11-12,16,19H,4-6,9-10,13-15H2,1-3H3,(H,25,31)(H2,26,27,30)/t16-,19-

HIDE SMILES / InChI

Molecular Formula	C24H34N4O5S
Molecular Weight	490.616
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description

Glimepiride, like glyburide and glipizide, is a "second-generation" sulfonylurea agents. Glimepiride is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin. The mechanism of action of glimepiride in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glimepiride likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin. Glimepiride is used for concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus. Glimepiride`s original trade name is Amaryl.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Acetylcholinesterase 207	Inhibitor 8,297	235.0 µM [IC50]
Cytochrome P450 2C9 50	Inhibitor 8,297	12.7 µM [IC50]
ATP-sensitive inward rectifier potassium channel 1 7	Inhibitor 8,297
Sulfonylurea receptor 1 5	Agonist 2,678	3.0 nM [IC50]
Potassium channel, inwardly rectifying, subfamily J, member 11 1	Inhibitor 8,297	400.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259	Primary		Approved 8,429	AMARYL

C_max

Value	Dose	Co-administered	Analyte	Population
551 ng/mL	8 mg single, oral		GLIMEPIRIDE plasma	Homo sapiens
74.05 μg/L	2 mg single, oral		GLIMEPIRIDE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
646.98 μg × h/L	2 mg single, oral		GLIMEPIRIDE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.3 h	8 mg single, oral		GLIMEPIRIDE plasma	Homo sapiens
4.08 h	2 mg single, oral		GLIMEPIRIDE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.5%	8 mg single, oral		GLIMEPIRIDE plasma	Homo sapiens

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1,037		inhibitor 1,612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A1 204 UGT1A3 84 UGT1A6 108 UGT1A9 116 UGT2B7 146 UGT2B15 64	OATP1B1 406

Drug as perpetrator

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Target	Modality	Activity
UGT1A1 254	inhibitor 3,277	yes [Inhibition 100 uM]
UGT1A3 93	inhibitor 3,277	yes [Inhibition 100 uM]
UGT1A6 141	inhibitor 3,277	yes [Inhibition 100 uM]
UGT1A9 121	inhibitor 3,277	yes [Inhibition 100 uM]
UGT2B15 64	inhibitor 3,277	yes [Inhibition 100 uM]

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Drug as victim

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Target	Modality	Activity	Metabolite	Clinical evidence
OATP1B1 406	substrate 3,367	yes
CYP2C9 1,037	substrate 3,367	yes		likely (co-administration study)

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1,647	inhibitor 1,626

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:5383	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:5383
ChemicalBook	CB8275358	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8275358
ChemicalBook	CB8318552	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB8318552
MolPort	MolPort-003-847-587	https://www.molport.com/shop/molecule-link/MolPort-003-847-587
Selleck Chemicals	Glimepiride	http://www.selleckchem.com/products/Glimepiride.html

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PubMed

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Title	Date	PubMed
Oral hypoglycemic agents: insulin secretagogues, alpha-glucosidase inhibitors and insulin sensitizers.	2001	11460577
Effects of fluconazole and fluvoxamine on the pharmacokinetics and pharmacodynamics of glimepiride.	2001 Apr	11309547
Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride.	2001 Nov	11719730
Predictors of response to glimepiride in patients with type 2 diabetes mellitus.	2001 Nov	11694855
Improved glycaemic control by addition of glimepiride to metformin monotherapy in type 2 diabetic patients.	2001 Oct	11678974

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Patents

Sample Use Guides

In Vivo Use Guide

The usual starting dose of AMARYL as initial therapy is 1-2 mg once daily, administered with breakfast or the first main meal. Those patients who may be more sensitive to hypoglycemic drugs should be started at 1 mg once daily, and should be titrated carefully.

Route of Administration: Oral

In Vitro Use Guide

Therapeutic concentrations of glimepiride (10 uM) block three types of recombinant KATP channel ± Kir6.2/SUR1, Kir6.2/SUR2A and Kir6.2/SUR2B (corresponding to the b-cell, cardiac and smooth muscle types of KATP channel)

Substance Class	Chemical
Record UNII	6KY687524K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

GLIMEPIRIDE

Official Name

English

Glimepiride [WHO-DD]

Common Name

English

GLIMEPIRIDE [ORANGE BOOK]

Common Name

English

AMARYL

Brand Name

English

GLIMEPIRIDE [USP-RS]

Common Name

English

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Classification Tree

Code System

Code

Urea

NDF-RT

N0000008054

Diabetes

LIVERTOX

459

Sulfones

NDF-RT

N0000008054

Combinations of oral blood glucose lowering drugs

WHO-VATC

QA10BD06

Sulfones

NDF-RT

N0000008054

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Code System

Code

Type

Description

ChEMBL

CHEMBL1481

PRIMARY

NCI_THESAURUS

C29073

PRIMARY

RXCUI

25789

PRIMARY

RxNorm

WIKIPEDIA

GLIMEPIRIDE

PRIMARY

RS_ITEM_NUM

1292303

PRIMARY

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Related Record

Type

Details


					6KY687524K

GLIMEPIRIDE

BASIS OF STRENGTH->SUBSTANCE

Interaction Type:

ASSAY (HPLC)

Qualification:

USP

Amount:

RELATIONSHIP_AMOUNT [98 to 102] WEIGHT PERCENT (limits)


					AIN96D6SGL

OATP1B1

TRANSPORTER -> SUBSTRATE

Comments:

Clearance of glimepiridein OATP1B1*5 and *15 was significantly reduced compared to the wild-type.

Amount:


					L9DP834D1P

CYTOCHROME P450 2C9

METABOLIC ENZYME -> SUBSTRATE

Comments:

Clearance of glimepiride CYP2C9*2 and *3 was significantly reduced compared to the wild-type.

Amount:


					6D53G0FD0Z

PLASMA PROTEIN FRACTION (HUMAN)

BINDER->LIGAND

Interaction Type:

BINDING

Amount:

99.5 % (average)


					8RT5G5EY5Z

ATP-BINDING CASSETTE SUB-FAMILY C MEMBER 8

TARGET -> INHIBITOR

Amount:

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Related Record

Type

Details


					WVY9QXS57P

HYDROXYGLIMEPIRIDE, TRANS-

METABOLITE LESS ACTIVE -> PARENT

Qualification:

URINE

Amount:

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Related Record

Type

Details


					24T6XIR2MZ

GLIMEPIRIDE, CIS-

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

RELATIONSHIP_AMOUNT [<0.8] PERCENT PEAK AREA (limits)


					A72YB30612

GLIMEPIRIDE URETHANE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

USP

Amount:

RELATIONSHIP_AMOUNT [<0.1] PERCENT PEAK AREA (limits)


					24T6XIR2MZ

GLIMEPIRIDE, CIS-

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

USP

Amount:

RELATIONSHIP_AMOUNT [<0.8] PERCENT PEAK AREA (limits)


					612913U5L6

GLIMEPIRIDE SULFONAMIDE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

USP

Amount:

RELATIONSHIP_AMOUNT [<0.4] PERCENT PEAK AREA (limits)


					612913U5L6

GLIMEPIRIDE SULFONAMIDE

IMPURITY -> PARENT

Interaction Type:

CHROMATOGRAPHIC PURITY (HPLC/UV)

Qualification:

EP

Amount:

RELATIONSHIP_AMOUNT [<0.4] PERCENT PEAK AREA (limits)

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Related Record

Type

Details


					6KY687524K

GLIMEPIRIDE

ACTIVE MOIETY

Amount:

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Name	Property Type	Amount
Volume of Distribution	PHARMACOKINETIC	0.13 Liters/Kilogram (average)

Biological Half-life	PHARMACOKINETIC	[5 to 9] hours (average)

SMILES

InChI

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator