U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS
This repository is under review for potential modification in compliance with Administration directives.

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 of NATEGLINIDE

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
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
125.0 µM [IC50]
946.0 µM [IC50]
8.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
5690 ng/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
10.45 mg × h/L
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
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.89 h
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
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
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

Doses

DosePopulationAdverse events​
3420 mg single, oral
Overdose
Dose: 3420 mg
Route: oral
Route: single
Dose: 3420 mg
Sources:
unknown, 30 years
Health Status: unknown
Age Group: 30 years
Sex: F
Sources:
Other AEs: Hypoglycemia...
Other AEs:
Hypoglycemia
Sources:
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:
unhealthy, 59 years (range: 42–67 years)
Health Status: unhealthy
Age Group: 59 years (range: 42–67 years)
Sex: M+F
Sources:
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:
unhealthy
Disc. AE: Hypoglycemia...
AEs leading to
discontinuation/dose reduction:
Hypoglycemia (0.3%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Hypoglycemia
3420 mg single, oral
Overdose
Dose: 3420 mg
Route: oral
Route: single
Dose: 3420 mg
Sources:
unknown, 30 years
Health Status: unknown
Age Group: 30 years
Sex: F
Sources:
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:
unhealthy
PubMed

PubMed

TitleDatePubMed
Pharmacokinetics and metabolism of nateglinide in humans.
2001 Apr
Nateglinide for type 2 diabetes.
2001 Apr 2
FDA approves nateglinide for treatment of type 2 diabetes.
2001 Feb 15
[New glucose regulator. More comfort for the type 2 diabetic patient].
2001 Feb 8
Mealtime glucose regulation with nateglinide in healthy volunteers: comparison with repaglinide and placebo.
2001 Jan
[Fasting blood glucose has little value. Postprandial glucose indicates risk].
2001 Jan 11
A new crystal form of nateglinide.
2001 Jul
Randomized dose ranging study of the reduction of fasting and postprandial glucose in type 2 diabetes by nateglinide (A-4166).
2001 Jul
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
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
[New drugs].
2001 Sep
Study of the insulinotropic effect of the novel antihyperglycemic agent KAD-1229 using HIT T15 cells, a hamster's insulinoma cell line.
2002
Control of post-prandial hyperglycemia--an essential part of good diabetes treatment and prevention of cardiovascular complications.
2002 Apr
[Differential type 2 diabetes therapy based on pathophysiological aspects].
2002 Aug
The effects of nateglinide following oral glucose load in impaired glucose tolerance subjects: rapid insulin stimulation by nateglinide in IGT subjects.
2002 Dec
Type 2 diabetes management.
2002 Jan
Improvement of glucose tolerance by nateglinide occurs through enhancement of early phase insulin secretion.
2002 Jan
Post-load hyperglycaemia-an inappropriate therapeutic target.
2002 Jan 12
The pathophysiologic basis of efficacy and clinical experience with the new oral antidiabetic agents.
2002 Jan-Feb
Efficacy and safety of nateglinide in the treatment of type II diabetes mellitus.
2002 Jul
Preventing the progressive nature of type 2 diabetes.
2002 Jul-Aug
Nateglinide improves glycaemic control when added to metformin monotherapy: results of a randomized trial with type 2 diabetes patients.
2002 May
[Glinides and glitazones in diabetes treatment. Are they really effective?].
2002 May 2
Nateglinide suppresses postprandial hypertriglyceridemia in Zucker fatty rats and Goto-Kakizaki rats: comparison with voglibose and glibenclamide.
2002 Nov
Decreased blood glucose excursion by nateglinide ameliorated neuropathic changes in Goto-Kakizaki rats, an animal model of non-obese type 2 diabetes.
2002 Nov
Transport and uptake of nateglinide in Caco-2 cells and its inhibitory effect on human monocarboxylate transporter MCT1.
2002 Oct
Efficacy, tolerability and safety of nateglinide in combination with metformin. Results from a study under general practice conditions.
2003 Aug
Pharmacokinetics of nateglinide and its metabolites in subjects with type 2 diabetes mellitus and renal failure.
2003 Aug
Pharmacokinetics of nateglinide in renally impaired diabetic patients.
2003 Feb
Pharmacodynamics, insulinotropic action and hypoglycemic effect of nateglinide and glibenclamide in normal and diabetic rats.
2003 Jan
Nateglinide (Starlix): update on a new antidiabetic agent.
2003 Jul-Aug
The role of oral antidiabetic agents: why and when to use an early-phase insulin secretion agent in Type II diabetes mellitus.
2003 Mar
Pharmacologic restoration of the early insulin response in pre-diabetic monkeys controls mealtime glucose excursions without peripheral hyperinsulinaemia.
2003 Mar
Patents

Sample Use Guides

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
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
  • Download
Name Type Language
STARSIS
Preferred Name English
NATEGLINIDE
EMA EPAR   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
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
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
NCI_THESAURUS C98079
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
NDF-RT N0000175448
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
WHO-ATC A10BX03
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
WHO-VATC QA10BX03
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
LIVERTOX NBK548227
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
Code System Code Type Description
ChEMBL
CHEMBL783
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
CHEBI
31897
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
CAS
105816-04-4
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
IUPHAR
6833
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
DAILYMED
41X3PWK4O2
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
MESH
C060142
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
WIKIPEDIA
NATEGLINIDE
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
USAN
MM-15
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
RXCUI
274332
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY RxNorm
SMS_ID
100000091326
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
EVMPD
SUB09170MIG
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
FDA UNII
41X3PWK4O2
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
LACTMED
Nateglinide
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
INN
7594
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
NCI_THESAURUS
C61858
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
MERCK INDEX
m7780
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY Merck Index
NSC
758695
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
RS_ITEM_NUM
1457607
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
DRUG BANK
DB00731
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
EPA CompTox
DTXSID9040687
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
DRUG CENTRAL
1886
Created by admin on Mon Mar 31 18:23:33 GMT 2025 , Edited by admin on Mon Mar 31 18:23:33 GMT 2025
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
ENANTIOMER -> ENANTIOMER
TRANSPORTER -> SUBSTRATE
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Volume of Distribution PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION