NATEGLINIDE

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 Search

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
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 6 Target ID: CHEMBL1971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21923736	Inhibitor 7728
Cytochrome P450 2C9 46 Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20609060	Inhibitor 7728	125.0 µM [IC50]
Cytochrome P450 2C19 49 Target ID: CHEMBL3622 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20609060	Inhibitor 7728	946.0 µM [IC50]
Sulfonylurea receptor 1, Kir6.2 12 Target ID: CHEMBL2096972 Sources: http://www.drugbank.ca/drugs/DB00731	Inhibitor 7728	8.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 240 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021204s014lbl.pdf	Primary		Approved 8043	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

C_max

Value	Dose	Co-administered	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

AUC

Value	Dose	Co-administered	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 unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	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 unknown	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

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 n = 1 Health Status: unknown Age Group: 30 years Sex: F Population Size: 1 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) n = 24 Health Status: unhealthy Condition: Type 2 diabetes Age Group: 59 years (range: 42–67 years) Sex: M+F Population Size: 24 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 n = 2600 Health Status: unhealthy Condition: Type 2 diabetes Population Size: 2600 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 n = 1 Health Status: unknown Age Group: 30 years Sex: F Population Size: 1 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 n = 2600 Health Status: unhealthy Condition: Type 2 diabetes Population Size: 2600 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
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
eMolecules	2725047	https://www.emolecules.com/cgi-bin/more?vid=2725047
eMolecules	902172	https://www.emolecules.com/cgi-bin/more?vid=902172

PubMed

Title	Date	PubMed
Effectiveness of nateglinide on in vitro insulin secretion from rat pancreatic islets desensitized to sulfonylureas.	2001	12369729
Glucose-dependent and glucose-sensitizing insulinotropic effect of nateglinide: comparison to sulfonylureas and repaglinide.	2001	12369728
A new crystal form of nateglinide.	2001 Jul	12585087
[Interrelations of the pancreas exocrine and endocrine functions in chronic alcohol pancreatitis].	2002	12503279
Insulin secretagogues.	2002	12365816
Study of the insulinotropic effect of the novel antihyperglycemic agent KAD-1229 using HIT T15 cells, a hamster's insulinoma cell line.	2002	12236048
[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
No effect of the novel antidiabetic agent nateglinide on the pharmacokinetics and anticoagulant properties of warfarin in healthy volunteers.	2002 Dec	12463731
Control of postprandial hyperglycemia: optimal use of short-acting insulin secretagogues.	2002 Dec	12453952
Nateglinide improves early insulin secretion and controls postprandial glucose excursions in a prediabetic population.	2002 Dec	12453951
[Detection of crystal polymorphs of nateglinide by DSC].	2002 Jan	12579899
New drugs 2002, part 1.	2002 Jan	12352750
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
[Glinides and glitazones in diabetes treatment. Are they really effective?].	2002 May 2	12422705
Therapeutic options for the management of type 2 diabetes mellitus.	2002 Nov	12437315
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
Effects of nateglinide and glibenclamide on postprandial lipid and glucose metabolism in type 2 diabetes.	2002 Nov-Dec	12469362
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	12462297
A 3-way crossover study to evaluate the pharmacokinetic interaction between nateglinide and diclofenac in healthy volunteers.	2002 Oct	12395978
Transport and uptake of nateglinide in Caco-2 cells and its inhibitory effect on human monocarboxylate transporter MCT1.	2002 Oct	12237260
[Management guideline for elderly diabetic patients].	2002 Sep	12387079
[Metformin--its regimen and effects].	2002 Sep	12387022
[Nateglinide].	2002 Sep	12387020
[Structures and mechanisms for non SU insulin secretagogues].	2002 Sep	12387019
[Adverse effects of oral hypoglycemic agents].	2002 Sep	12387013
Efficacy and safety of nateglinide in type 2 diabetic patients with modest fasting hyperglycemia.	2002 Sep	12213867
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
[symbol: see text] Nateglinide and [symbol: see text] repaglinide for type 2 diabetes?	2003 Jul	12879789
[Nateglinide and mitiglinide].	2003 Jul	12877090
[Pharmacological treatment of postprandial hyperglycemia in hypertensive patients with type 2 diabetes mellitus].	2003 Jul	12877088
Effect of fluconazole on the pharmacokinetics and pharmacodynamics of nateglinide.	2003 Jul	12844132
Efficacy and safety of combination therapy: repaglinide plus metformin versus nateglinide plus metformin.	2003 Jul	12832314
Should diabetic patients treated long-term with sulfonylureas be switched to nateglinide?	2003 Jul 28	12885691
Nateglinide (Starlix): update on a new antidiabetic agent.	2003 Jul-Aug	12918894
[Meglitinide analogs: new insulinotropic agents for the treatment of non-insulin dependent diabetes].	2003 Jun	12891883
The effect of nateglinide taken with food on gastric emptying rates in healthy subjects.	2003 Jun	12860494
Rationale and options for combination therapy in the treatment of Type 2 diabetes.	2003 Mar	12652358
The mechanisms underlying the unique pharmacodynamics of nateglinide.	2003 Mar	12652357
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
Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety, specifically inhibits pancreatic beta-cell-type K(ATP) channels.	2003 Mar	12604678
Hypoglycemia due to nateglinide administration in diabetic patient with chronic renal failure.	2003 Mar	12590015
The prevention of type 2 diabetes--lifestyle change or pharmacotherapy? A challenge for the 21st century.	2003 Mar	12590013
Rapid and simple method for the analysis of nateglinide in human plasma using HPLC analysis with UV detection.	2003 Mar 10	12615243

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 `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

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Name

Type

Language

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

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