U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C19H27NO3
Molecular Weight 317.4233
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NATEGLINIDE

SMILES

CC(C)[C@]1([H])CC[C@]([H])(CC1)C(=N[C@]([H])(Cc2ccccc2)C(=O)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 317.4233
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
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

9.7735678E11
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
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 unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
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 unknown
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
3420 mg single, oral
Overdose
Dose: 3420 mg
Route: oral
Route: single
Dose: 3420 mg
Sources:
unknown, 30 years
n = 1
Health Status: unknown
Age Group: 30 years
Sex: F
Population Size: 1
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)
n = 24
Health Status: unhealthy
Condition: Type 2 diabetes
Age Group: 59 years (range: 42–67 years)
Sex: M+F
Population Size: 24
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
n = 2600
Health Status: unhealthy
Condition: Type 2 diabetes
Population Size: 2600
Sources:
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
n = 1
Health Status: unknown
Age Group: 30 years
Sex: F
Population Size: 1
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
n = 2600
Health Status: unhealthy
Condition: Type 2 diabetes
Population Size: 2600
Sources:
PubMed

PubMed

TitleDatePubMed
Effectiveness of nateglinide on in vitro insulin secretion from rat pancreatic islets desensitized to sulfonylureas.
2001
Glucose-dependent and glucose-sensitizing insulinotropic effect of nateglinide: comparison to sulfonylureas and repaglinide.
2001
A new crystal form of nateglinide.
2001 Jul
[Interrelations of the pancreas exocrine and endocrine functions in chronic alcohol pancreatitis].
2002
Insulin secretagogues.
2002
Study of the insulinotropic effect of the novel antihyperglycemic agent KAD-1229 using HIT T15 cells, a hamster's insulinoma cell line.
2002
[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
No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers.
2002 Dec
Control of postprandial hyperglycemia: optimal use of short-acting insulin secretagogues.
2002 Dec
Nateglinide improves early insulin secretion and controls postprandial glucose excursions in a prediabetic population.
2002 Dec
[Detection of crystal polymorphs of nateglinide by DSC].
2002 Jan
New drugs 2002, part 1.
2002 Jan
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
[Glinides and glitazones in diabetes treatment. Are they really effective?].
2002 May 2
Therapeutic options for the management of type 2 diabetes mellitus.
2002 Nov
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
Effects of nateglinide and glibenclamide on postprandial lipid and glucose metabolism in type 2 diabetes.
2002 Nov-Dec
Health and economic effects of adding nateglinide to metformin to achieve dual control of glycosylated hemoglobin and postprandial glucose levels in a model of type 2 diabetes mellitus.
2002 Oct
A 3-way crossover study to evaluate the pharmacokinetic interaction between nateglinide and diclofenac in healthy volunteers.
2002 Oct
Transport and uptake of nateglinide in Caco-2 cells and its inhibitory effect on human monocarboxylate transporter MCT1.
2002 Oct
[Management guideline for elderly diabetic patients].
2002 Sep
[Metformin--its regimen and effects].
2002 Sep
[Nateglinide].
2002 Sep
[Structures and mechanisms for non SU insulin secretagogues].
2002 Sep
[Adverse effects of oral hypoglycemic agents].
2002 Sep
Efficacy and safety of nateglinide in type 2 diabetic patients with modest fasting hyperglycemia.
2002 Sep
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
[symbol: see text] Nateglinide and [symbol: see text] repaglinide for type 2 diabetes?
2003 Jul
[Nateglinide and mitiglinide].
2003 Jul
[Pharmacological treatment of postprandial hyperglycemia in hypertensive patients with type 2 diabetes mellitus].
2003 Jul
Effect of fluconazole on the pharmacokinetics and pharmacodynamics of nateglinide.
2003 Jul
Efficacy and safety of combination therapy: repaglinide plus metformin versus nateglinide plus metformin.
2003 Jul
Should diabetic patients treated long-term with sulfonylureas be switched to nateglinide?
2003 Jul 28
Nateglinide (Starlix): update on a new antidiabetic agent.
2003 Jul-Aug
[Meglitinide analogs: new insulinotropic agents for the treatment of non-insulin dependent diabetes].
2003 Jun
The effect of nateglinide taken with food on gastric emptying rates in healthy subjects.
2003 Jun
Rationale and options for combination therapy in the treatment of Type 2 diabetes.
2003 Mar
The mechanisms underlying the unique pharmacodynamics of nateglinide.
2003 Mar
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
Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety, specifically inhibits pancreatic beta-cell-type K(ATP) channels.
2003 Mar
Hypoglycemia due to nateglinide administration in diabetic patient with chronic renal failure.
2003 Mar
The prevention of type 2 diabetes--lifestyle change or pharmacotherapy? A challenge for the 21st century.
2003 Mar
Rapid and simple method for the analysis of nateglinide in human plasma using HPLC analysis with UV detection.
2003 Mar 10
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 Fri Jun 25 20:35:43 UTC 2021
Edited
by admin
on Fri Jun 25 20:35:43 UTC 2021
Record UNII
41X3PWK4O2
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
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
STARSIS
Brand 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 [WHO-DD]
Common Name English
NATEGLINIDE [EMA EPAR]
Common Name English
NATEGLINIDE [USP]
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 Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
NCI_THESAURUS C98079
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
NDF-RT N0000175448
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
WHO-ATC A10BX03
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
WHO-VATC QA10BX03
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
LIVERTOX 671
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL783
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
CAS
105816-04-4
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
IUPHAR
6833
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
MESH
C060142
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
WIKIPEDIA
NATEGLINIDE
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
RXCUI
274332
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY RxNorm
EVMPD
SUB09170MIG
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
FDA UNII
41X3PWK4O2
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
LACTMED
Nateglinide
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
INN
7594
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
NCI_THESAURUS
C61858
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
USP_CATALOG
1457607
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY USP-RS
MERCK INDEX
M7780
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY Merck Index
DRUG BANK
DB00731
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
EPA CompTox
105816-04-4
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
DRUG CENTRAL
1886
Created by admin on Fri Jun 25 20:35:43 UTC 2021 , Edited by admin on Fri Jun 25 20:35:43 UTC 2021
PRIMARY
Related Record Type Details
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
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
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