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 8228
Cytochrome P450 2C9 50 Target ID: CHEMBL3397 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20609060	Inhibitor 8228	125.0 µM [IC50]
Cytochrome P450 2C19 51 Target ID: CHEMBL3622 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20609060	Inhibitor 8228	946.0 µM [IC50]
Sulfonylurea receptor 1, Kir6.2 13 Target ID: CHEMBL2096972 Sources: http://www.drugbank.ca/drugs/DB00731	Inhibitor 8228	8.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 256 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021204s014lbl.pdf	Primary		Approved 8360	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
Glucose-dependent and glucose-sensitizing insulinotropic effect of nateglinide: comparison to sulfonylureas and repaglinide.	2001	12369728
Early insulin release effectively improves glucose tolerance: studies in two rodent models of type 2 diabetes mellitus.	2001 Apr	11298730
Mealtime glucose regulation with nateglinide in healthy volunteers: comparison with repaglinide and placebo.	2001 Jan	11194245
Postoperative management of the diabetic patient.	2001 Sep	11565495
Improvement of glucose tolerance by nateglinide occurs through enhancement of early phase insulin secretion.	2002 Jan	11782867
Gateways to clinical trials.	2002 Jan-Feb	11980386
The pathophysiologic basis of efficacy and clinical experience with the new oral antidiabetic agents.	2002 Jan-Feb	11872380
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	12088930
[Metformin--its regimen and effects].	2002 Sep	12387022
Treatment of patients over 64 years of age with type 2 diabetes: experience from nateglinide pooled database retrospective analysis.	2003 Jul	12832316
Addition of nateglinide to rosiglitazone monotherapy suppresses mealtime hyperglycemia and improves overall glycemic control.	2003 Jun	12766094
Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety, specifically inhibits pancreatic beta-cell-type K(ATP) channels.	2003 Mar	12604678

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 `Wed Jul 05 23:43:14 UTC 2023` Edited by `admin` on `Wed Jul 05 23:43:14 UTC 2023`
Record UNII	41X3PWK4O2
Record Status	`Validated (UNII)`
Record Version

Download

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 [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