NATEGLINIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H27NO3
Molecular Weight	317.4226
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)[C@H]1CC[C@@H](CC1)C(=O)N[C@H](CC2=CC=CC=C2)C(O)=O

InChI

InChIKey=OELFLUMRDSZNSF-BRWVUGGUSA-N

InChI=1S/C19H27NO3/c1-13(2)15-8-10-16(11-9-15)18(21)20-17(19(22)23)12-14-6-4-3-5-7-14/h3-7,13,15-17H,8-12H2,1-2H3,(H,20,21)(H,22,23)/t15-,16-,17-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C19H27NO3
Molecular Weight	317.4226
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugbank.ca/drugs/DB00731
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021204s014lbl.pdf https://www.ncbi.nlm.nih.gov/pubmed/12764427

Nateglinide is an oral antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus (NIDDM). It belongs to the meglitinide class of short-acting insulin secretagogues, which act by binding to β cells of the pancreas to stimulate insulin release. Nateglinide is an amino acid derivative that induces an early insulin response to meals decreasing postprandial blood glucose levels. It should only be taken with meals and meal-time doses should be skipped with any skipped meal. Approximately one month of therapy is required before a decrease in fasting blood glucose is seen. Meglitnides may have a neutral effect on weight or cause a slight increase in weight. The average weight gain caused by meglitinides appears to be lower than that caused by sulfonylureas and insulin and appears to occur only in those naïve to oral antidiabetic agents. Due to their mechanism of action, meglitinides may cause hypoglycemia although the risk is thought to be lower than that of sulfonylureas since their action is dependent on the presence of glucose. In addition to reducing postprandial and fasting blood glucose, meglitnides have been shown to decrease glycosylated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Meglitinides appear to be more effective at lowering postprandial blood glucose than metformin, sulfonylureas and thiazolidinediones. Nateglinide is extensively metabolized in the liver and excreted in urine (83%) and feces (10%). The major metabolites possess less activity than the parent compound. One minor metabolite, the isoprene, has the same potency as its parent compound.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Sulfonylurea receptor 2 9 Target ID: CHEMBL1971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21923736	Inhibitor 8504
Cytochrome P450 2C9 50 Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20609060	Inhibitor 8504	125.0 µM [IC50]
Cytochrome P450 2C19 51 Target ID: CHEMBL3622 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20609060	Inhibitor 8504	946.0 µM [IC50]
Sulfonylurea receptor 1, Kir6.2 13 Target ID: CHEMBL2096972 Sources: http://www.drugbank.ca/drugs/DB00731	Inhibitor 8504	8.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 262 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021204s014lbl.pdf	Primary		Approved 8583	Starlix Approved Use Starlix® (nateglinide) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Launch Date 2000

C_max

Value	Dose	Analyte	Population
5690 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/11259325	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	NATEGLINIDE blood	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
16.19 μg/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-204_Stsrlix_biopharmr.pdf	120 mg single, intravenous dose: 120 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NATEGLINIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5.21 μg/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-204_Stsrlix_biopharmr.pdf	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	NATEGLINIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
10.45 mg × h/L EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12940610	90 mg single, oral dose: 90 mg route of administration: Oral experiment type: SINGLE co-administered:	NATEGLINIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
17.72 μg × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-204_Stsrlix_biopharmr.pdf	120 mg single, intravenous dose: 120 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NATEGLINIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
13.33 μg × h/mL REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-204_Stsrlix_biopharmr.pdf	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	NATEGLINIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
1.89 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/12940610	90 mg single, oral dose: 90 mg route of administration: Oral experiment type: SINGLE co-administered:	NATEGLINIDE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.88 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-204_Stsrlix_biopharmr.pdf	120 mg single, intravenous dose: 120 mg route of administration: Intravenous experiment type: SINGLE co-administered:	NATEGLINIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1.58 h REVIEW https://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/21-204_Stsrlix_biopharmr.pdf	120 mg single, oral dose: 120 mg route of administration: Oral experiment type: SINGLE co-administered:	NATEGLINIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
3420 mg single, oral Overdose Dose: 3420 mg Route: oral Route: single Dose: 3420 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15616260	unknown, 30 years Health Status: unknown Age Group: 30 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15616260	Other AEs: Hypoglycemia... Other AEs: Hypoglycemia Sources: https://pubmed.ncbi.nlm.nih.gov/15616260
240 mg 3 times / day steady, oral Highest studied dose Dose: 240 mg, 3 times / day Route: oral Route: steady Dose: 240 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/10720043	unhealthy, 59 years (range: 42–67 years) Health Status: unhealthy Age Group: 59 years (range: 42–67 years) Sex: M+F Sources: https://pubmed.ncbi.nlm.nih.gov/10720043	Sources: https://pubmed.ncbi.nlm.nih.gov/10720043
120 mg 3 times / day steady, oral Recommended Dose: 120 mg, 3 times / day Route: oral Route: steady Dose: 120 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/077463s000lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/077463s000lbl.pdf	Disc. AE: Hypoglycemia... AEs leading to discontinuation/dose reduction: Hypoglycemia (0.3%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/077463s000lbl.pdf

AEs

AE	Significance	Dose	Population
Hypoglycemia		3420 mg single, oral Overdose Dose: 3420 mg Route: oral Route: single Dose: 3420 mg Sources: https://pubmed.ncbi.nlm.nih.gov/15616260	unknown, 30 years Health Status: unknown Age Group: 30 years Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/15616260
Hypoglycemia	0.3% Disc. AE	120 mg 3 times / day steady, oral Recommended Dose: 120 mg, 3 times / day Route: oral Route: steady Dose: 120 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/077463s000lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/077463s000lbl.pdf

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:31897	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:31897
ChemicalBook	CB9472923	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9472923
eMolecules	2725047	https://www.emolecules.com/cgi-bin/more?vid=2725047
eMolecules	902172	https://www.emolecules.com/cgi-bin/more?vid=902172
MolPort	MolPort-003-986-201	https://www.molport.com/shop/molecule-link/MolPort-003-986-201
Selleck Chemicals	Nateglinide(Starlix)	http://www.selleckchem.com/products/Nateglinide(Starlix).html
ZINC	ZINC000101489663	http://zinc15.docking.org/substances/ZINC000101489663

PubMed

Title	Date	PubMed
Pharmacokinetics and metabolism of nateglinide in humans.	2001 Apr	11259325
Nateglinide for type 2 diabetes.	2001 Apr 2	11283474
FDA approves nateglinide for treatment of type 2 diabetes.	2001 Feb 15	11225164
[New glucose regulator. More comfort for the type 2 diabetic patient].	2001 Feb 8	11247371
Mealtime glucose regulation with nateglinide in healthy volunteers: comparison with repaglinide and placebo.	2001 Jan	11194245
[Fasting blood glucose has little value. Postprandial glucose indicates risk].	2001 Jan 11	11216017
A new crystal form of nateglinide.	2001 Jul	12585087
Randomized dose ranging study of the reduction of fasting and postprandial glucose in type 2 diabetes by nateglinide (A-4166).	2001 Jul	11423506
The effects of mitiglinide (KAD-1229), a new anti-diabetic drug, on ATP-sensitive K+ channels and insulin secretion: comparison with the sulfonylureas and nateglinide.	2001 Nov 9	11716850
Effects of timing of administration and meal composition on the pharmacokinetic and pharmacodynamic characteristics of the short-acting oral hypoglycemic agent nateglinide in healthy subjects.	2001 Oct	11600556
[New drugs].	2001 Sep	11680207
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
[Differential type 2 diabetes therapy based on pathophysiological aspects].	2002 Aug	12235731
The effects of nateglinide following oral glucose load in impaired glucose tolerance subjects: rapid insulin stimulation by nateglinide in IGT subjects.	2002 Dec	12625415
Type 2 diabetes management.	2002 Jan	11823724
Improvement of glucose tolerance by nateglinide occurs through enhancement of early phase insulin secretion.	2002 Jan	11782867
Post-load hyperglycaemia-an inappropriate therapeutic target.	2002 Jan 12	11809285
The pathophysiologic basis of efficacy and clinical experience with the new oral antidiabetic agents.	2002 Jan-Feb	11872380
Efficacy and safety of nateglinide in the treatment of type II diabetes mellitus.	2002 Jul	12674176
Preventing the progressive nature of type 2 diabetes.	2002 Jul-Aug	12402899
Nateglinide improves glycaemic control when added to metformin monotherapy: results of a randomized trial with type 2 diabetes patients.	2002 May	12047396
[Glinides and glitazones in diabetes treatment. Are they really effective?].	2002 May 2	12422705
Nateglinide suppresses postprandial hypertriglyceridemia in Zucker fatty rats and Goto-Kakizaki rats: comparison with voglibose and glibenclamide.	2002 Nov	12419950
Decreased blood glucose excursion by nateglinide ameliorated neuropathic changes in Goto-Kakizaki rats, an animal model of non-obese type 2 diabetes.	2002 Nov	12404197
Transport and uptake of nateglinide in Caco-2 cells and its inhibitory effect on human monocarboxylate transporter MCT1.	2002 Oct	12237260
Efficacy, tolerability and safety of nateglinide in combination with metformin. Results from a study under general practice conditions.	2003 Aug	12951631
Pharmacokinetics of nateglinide and its metabolites in subjects with type 2 diabetes mellitus and renal failure.	2003 Aug	12940610
Pharmacokinetics of nateglinide in renally impaired diabetic patients.	2003 Feb	12616669
Pharmacodynamics, insulinotropic action and hypoglycemic effect of nateglinide and glibenclamide in normal and diabetic rats.	2003 Jan	12469228
Nateglinide (Starlix): update on a new antidiabetic agent.	2003 Jul-Aug	12918894
The role of oral antidiabetic agents: why and when to use an early-phase insulin secretion agent in Type II diabetes mellitus.	2003 Mar	12652356
Pharmacologic restoration of the early insulin response in pre-diabetic monkeys controls mealtime glucose excursions without peripheral hyperinsulinaemia.	2003 Mar	12652355

Patents

Sample Use Guides

In Vivo Use Guide

The recommended starting and maintenance dose of Starlix, alone or in combination with metformin or a thiazolidinedione, is 120 mg three times daily before meals. The 60-mg dose of Starlix, either alone or in combination with metformin or a thiazolidinedione, may be used in patients who are near goal HbA1C when treatment is initiated.

Route of Administration: Oral

In Vitro Use Guide

Nateglinide inhibits Kir6.2/SUR1 and Kir6.2/SUR2B channels at 100 nM, and inhibits Kir6.2/SUR2A channels at high concentrations (1 uM).

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:23:33 GMT 2025` Edited by `admin` on `Mon Mar 31 18:23:33 GMT 2025`
Record UNII	41X3PWK4O2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

STARSIS

Preferred Name

English

NATEGLINIDE

Official Name

English

NATEGLINIDE [EP MONOGRAPH]

Common Name

English

DJN 608

Code

English

NATEGLINIDE [VANDF]

Common Name

English

NATEGLINIDE [USAN]

Common Name

English

D-PHENYLALANINE, N-((TRANS-4-(1-METHYLETHYL)CYCLOHEXYL)CARBONYL)-

Systematic Name

English

NATEGLINIDE [ORANGE BOOK]

Common Name

English

NATEGLINIDE [USP MONOGRAPH]

Common Name

English

SDZ-DJN-608

Code

English

NATEGLINIDE [USP-RS]

Common Name

English

SDZ DJN 608

Code

English

STARLIX

Brand Name

English

DJN-608

Code

English

NATEGLINIDE [MI]

Common Name

English

D-NATEGLINIDE

Common Name

English

NSC-758695

Code

English

NATEGLINIDE [MART.]

Common Name

English

AY-4166

Code

English

nateglinide [INN]

Common Name

English

NATEGLINIDE [EMA EPAR]

Common Name

English

Nateglinide [WHO-DD]

Common Name

English

SENAGLINIDE

Common Name

English

A-4166

Code

English

NATEGLINIDE [JAN]

Common Name

English

Classification Tree Code System Code

NDF-RT

N0000175428