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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 L-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-ULQDDVLXSA-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-/m0/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

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
[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
Control of post-prandial hyperglycemia--an essential part of good diabetes treatment and prevention of cardiovascular complications.
2002 Apr
[Postprandial hyperglycemia. II. Pharmacological approaches].
2002 Apr
[Differential type 2 diabetes therapy based on pathophysiological aspects].
2002 Aug
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
Nateglinide, but not repaglinide, stimulates growth hormone release in rat pituitary cells by inhibition of K channels and stimulation of cyclic AMP-dependent exocytosis.
2002 Jul
Preventing the progressive nature of type 2 diabetes.
2002 Jul-Aug
[Islands cells are not activated quickly enough. Risk of obstruction of blood vessels].
2002 Jun 27
[Glinides and glitazones in diabetes treatment. Are they really effective?].
2002 May 2
[Dangerous postprandial glucose peaks. Risk for heart and blood vessels].
2002 May 23
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
Differential interactions of nateglinide and repaglinide on the human beta-cell sulphonylurea receptor 1.
2002 Sep
Combination therapy with nateglinide and a thiazolidinedione improves glycemic control in type 2 diabetes.
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
Pharmacodynamics, insulinotropic action and hypoglycemic effect of nateglinide and glibenclamide in normal and diabetic rats.
2003 Jan
[Nateglinide and mitiglinide].
2003 Jul
Effect of fluconazole on the pharmacokinetics and pharmacodynamics of nateglinide.
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
Addition of nateglinide to rosiglitazone monotherapy suppresses mealtime hyperglycemia and improves overall glycemic control.
2003 Jun
Evaluation of the effects of nateglinide on postprandial glycemia in patients with type 2 diabetes mellitus: a multicenter, multinational, non-randomized, non-controlled Latin American study.
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
Hypoglycemia due to nateglinide administration in diabetic patient with chronic renal failure.
2003 Mar
[Differences between oral antidiabetics].
2003 Mar 20
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 Jul 07 00:15:57 UTC 2023
Edited
by admin
on Fri Jul 07 00:15:57 UTC 2023
Record UNII
E9V3S85RHY
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
L-NATEGLINIDE
Common Name English
L-PHENYLALANINE, N-((4-(1-METHYLETHYL)CYCLOHEXYL)CARBONYL)-, TRANS-
Systematic Name English
L-PHENYLALANINE, N-((TRANS-4-(1-METHYLETHYL)CYCLOHEXYL)CARBONYL)-
Systematic Name English
NATEGLINIDE IMPURITY B [EP IMPURITY]
Common Name English
N-((TRANS-4-(1-METHYLETHYL)CYCLOHEXYL)CARBONYL)-L-PHENYLALANINE
Common Name English
Code System Code Type Description
RS_ITEM_NUM
1457629
Created by admin on Fri Jul 07 00:15:57 UTC 2023 , Edited by admin on Fri Jul 07 00:15:57 UTC 2023
PRIMARY
FDA UNII
E9V3S85RHY
Created by admin on Fri Jul 07 00:15:57 UTC 2023 , Edited by admin on Fri Jul 07 00:15:57 UTC 2023
PRIMARY
CAS
105816-05-5
Created by admin on Fri Jul 07 00:15:57 UTC 2023 , Edited by admin on Fri Jul 07 00:15:57 UTC 2023
PRIMARY
Related Record Type Details
ENANTIOMER -> ENANTIOMER
Related Record Type Details
PARENT -> IMPURITY
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP