Identification

Name
Nateglinide
Accession Number
DB00731  (APRD00593)
Type
Small Molecule
Groups
Approved, Investigational
Description

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.

Structure
Thumb
Synonyms
  • nateglinida
External IDs
A-4166 / AY-4166 / AY4166 / DJN 608 / DJN-608 / SDZ DJN 608 / SDZ-DJN-608
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
StarlixTablet, film coated60 mgOralNovartis Europharm Limited2001-04-03Not applicableEu
StarlixTablet, film coated120 mgOralNovartis Europharm Limited2001-04-03Not applicableEu
StarlixTablet60 mg/1OralNovartis Pharmaceuticals Corporation2000-12-04Not applicableUs00078 0351 05 nlmimage10 6c163601
StarlixTablet, film coated120 mgOralNovartis Europharm Limited2001-04-03Not applicableEu
StarlixTablet120 mg/1OralCaremark L.L.C.2002-09-122012-02-29Us
StarlixTablet, film coated120 mgOralNovartis Europharm Limited2001-04-03Not applicableEu
StarlixTablet, film coated180 mgOralNovartis Europharm Limited2001-04-03Not applicableEu
StarlixTablet, film coated60 mgOralNovartis Europharm Limited2001-04-03Not applicableEu
StarlixTablet, film coated180 mgOralNovartis Europharm Limited2001-04-03Not applicableEu
StarlixTablet, film coated60 mgOralNovartis Europharm Limited2001-04-03Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
NateglinideTablet60 mg/1OralDr Reddy's Laboratories2009-09-09Not applicableUs
NateglinideTablet, film coated60 mg/1OralZydus Pharmaceuticals Usa, Inc.2016-10-27Not applicableUs
NateglinideTablet, coated120 mg/1OralAv Kare, Inc.2016-04-06Not applicableUs
NateglinideTablet, coated120 mg/1OralPhysicians Total Care, Inc.2011-05-03Not applicableUs
NateglinideTablet, coated120 mg/1OralGolden State Medical Supply2015-09-10Not applicableUs
NateglinideTablet120 mg/1OralActavis Pharma Company2011-05-18Not applicableUs
NateglinideTablet, coated60 mg/1OralAmerincan Health Packaging2011-01-05Not applicableUs
NateglinideTablet, coated60 mg/1OralPar Pharmaceutical2009-09-08Not applicableUs
NateglinideTablet, coated120 mg/1OralNcs Health Care Of Ky, Inc Dba Vangard Labs2009-09-08Not applicableUs
NateglinideTablet, film coated120 mg/1OralCadila Pharnmaceuticals2016-10-27Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
TrazecNateglinide (60 mg)Tablet, film coatedOralNovartis Europharm Limited2001-04-032009-08-14Eu
TrazecNateglinide (180 mg)Tablet, film coatedOralNovartis Europharm Limited2001-04-032009-08-14Eu
TrazecNateglinide (60 mg)Tablet, film coatedOralNovartis Europharm Limited2001-04-032009-08-14Eu
TrazecNateglinide (180 mg)Tablet, film coatedOralNovartis Europharm Limited2001-04-032009-08-14Eu
TrazecNateglinide (120 mg)Tablet, film coatedOralNovartis Europharm Limited2001-04-032009-08-14Eu
TrazecNateglinide (120 mg)Tablet, film coatedOralNovartis Europharm Limited2001-04-032009-08-14Eu
TrazecNateglinide (60 mg)Tablet, film coatedOralNovartis Europharm Limited2001-04-032009-08-14Eu
TrazecNateglinide (180 mg)Tablet, film coatedOralNovartis Europharm Limited2001-04-032009-08-14Eu
TrazecNateglinide (120 mg)Tablet, film coatedOralNovartis Europharm Limited2001-04-032009-08-14Eu
TrazecNateglinide (60 mg)Tablet, film coatedOralNovartis Europharm Limited2001-04-032009-08-14Eu
International/Other Brands
Fastic / Starsis
Categories
UNII
41X3PWK4O2
CAS number
105816-04-4
Weight
Average: 317.429
Monoisotopic: 317.199093733
Chemical Formula
C19H27NO3
InChI Key
OELFLUMRDSZNSF-BRWVUGGUSA-N
InChI
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
IUPAC Name
(2R)-2-({hydroxy[(1r,4r)-4-(propan-2-yl)cyclohexyl]methylidene}amino)-3-phenylpropanoic acid
SMILES
[H][C@](CC1=CC=CC=C1)(N=C(O)[C@@]1([H])CC[C@@]([H])(CC1)C(C)C)C(O)=O

Pharmacology

Indication

For the treatment of non-insulin dependent-diabetes mellitus in conjunction with diet and exercise.

Associated Conditions
Pharmacodynamics

Insulin secretion by pancreatic β cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Nateglinide increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.

Mechanism of action

Nateglinide activity is dependent on the presence functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, nateglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, nateglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of nateglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Nateglinide appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.

TargetActionsOrganism
AATP-binding cassette sub-family C member 8
inhibitor
Human
UPeroxisome proliferator-activated receptor gamma
agonist
Human
Absorption

Rapidly absorbed following oral administration prior to a meal, absolute bioavailability is estimated to be approximately 73%. Peak plasma concentrations generally occur within 1 hour of oral administration. Onset of action is <20 minutes and the duration of action is approximately 4 hours.

Volume of distribution

10 liters in healthy subjects

Protein binding

98% bound to serum proteins, primarily serum albumin and to a lesser extent α1 acid glycoprotein

Metabolism

Hepatic, via cytochrome P450 isoenzymes CYP2C9 (70%) and CYP3A4 (30%). Metabolism is via hydroxylation followed by glucuronidation. The major metabolites have less antidiabetic activity than nateglinide, but the isoprene minor metabolite has antidiabetic activity comparable to that of nateglinide.

Route of elimination

Urine (83%) and feces (10%)

Half life

1.5 hours

Clearance
Not Available
Toxicity

An overdose may result in an exaggerated glucose-lowering effect with the development of hypoglycemic symptoms.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Nateglinide Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Nateglinide.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Nateglinide.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Nateglinide is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Nateglinide.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Nateglinide.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Nateglinide.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Nateglinide can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Nateglinide.
6-Deoxyerythronolide BThe metabolism of Nateglinide can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Nateglinide.
Food Interactions
  • Take upto 30 minutes before meals.

References

Synthesis Reference

Michito Sumikawa, "Methods for producing nateglinide B-type crystals." U.S. Patent US20030229249, issued December 11, 2003.

US20030229249
General References
Not Available
External Links
Human Metabolome Database
HMDB14869
KEGG Drug
D01111
KEGG Compound
C12508
PubChem Compound
5311309
PubChem Substance
46504836
ChemSpider
10482084
BindingDB
50344967
ChEBI
31897
ChEMBL
CHEMBL783
Therapeutic Targets Database
DAP000918
PharmGKB
PA450600
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Nateglinide
ATC Codes
A10BX03 — Nateglinide
FDA label
Download (56.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers3
2, 3CompletedTreatmentType 2 Diabetes Mellitus1
3CompletedTreatmentType 2 Diabetes Mellitus1
4CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
4CompletedTreatmentInsulin Resistance / Type 2 Diabetes Mellitus1
4CompletedTreatmentPosttransplant Diabetes Mellitus / Posttransplant Impaired Glucose Tolerance / Renal Transplant Recipient Patients1
4CompletedTreatmentType 2 Diabetes Mellitus5
4Unknown StatusPreventionImpaired Fasting Glucose (IFG) / Insulin Resistance1
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus3

Pharmacoeconomics

Manufacturers
  • Dr reddys laboratories ltd
  • Par pharmaceutical inc
  • Teva pharmaceuticals usa
  • Novartis pharmaceuticals corp
Packagers
  • Caremark LLC
  • Doctor Reddys Laboratories Ltd.
  • Heartland Repack Services LLC
  • Mckesson Corp.
  • Novartis AG
  • Par Pharmaceuticals
  • Physicians Total Care Inc.
  • Resource Optimization and Innovation LLC
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
TabletOral60 mg/1
Tablet, coatedOral120 mg/1
Tablet, coatedOral60 mg/1
Tablet, film coatedOral120 mg/1
Tablet, film coatedOral60 mg/1
TabletOral120 mg/1
Tablet, film coatedOral120 mg
Tablet, film coatedOral180 mg
Tablet, film coatedOral60 mg
TabletOral120 mg
TabletOral180 mg
TabletOral60 mg
Prices
Unit descriptionCostUnit
Starlix 120 mg tablet2.12USD tablet
Starlix 60 mg tablet2.01USD tablet
Nateglinide 120 mg tablet1.73USD tablet
Nateglinide 60 mg tablet1.66USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
USRE34878No1992-09-082009-09-08Us
CA2271865No2003-10-142017-11-14Canada
CA2114678No1999-04-272014-02-01Canada
US6559188No2000-09-152020-09-15Us
US6641841No1997-11-142017-11-14Us
US6844008No1997-11-142017-11-14Us
US6878749No2000-09-152020-09-15Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubilityPractically insolubleNot Available
logP2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00688 mg/mLALOGPS
logP3.82ALOGPS
logP4.85ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)4.06ChemAxon
pKa (Strongest Basic)1.53ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area69.89 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity89.98 m3·mol-1ChemAxon
Polarizability35.76 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier+0.7539
Caco-2 permeable-0.7148
P-glycoprotein substrateSubstrate0.6187
P-glycoprotein inhibitor INon-inhibitor0.8842
P-glycoprotein inhibitor IINon-inhibitor0.8604
Renal organic cation transporterNon-inhibitor0.8882
CYP450 2C9 substrateNon-substrate0.7192
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5103
CYP450 1A2 substrateNon-inhibitor0.9167
CYP450 2C9 inhibitorNon-inhibitor0.8412
CYP450 2D6 inhibitorNon-inhibitor0.9088
CYP450 2C19 inhibitorNon-inhibitor0.8764
CYP450 3A4 inhibitorNon-inhibitor0.8874
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8734
Ames testNon AMES toxic0.922
CarcinogenicityNon-carcinogens0.9354
BiodegradationNot ready biodegradable0.7779
Rat acute toxicity2.0362 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9881
hERG inhibition (predictor II)Non-inhibitor0.8425
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-0009000000-6d3ecfcb5cad6574fb53
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014i-2906000000-611e57a755195a18f161
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0297-4900000000-249affd02e2091b02c4f
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00kg-6900000000-75cf7590825f0daed817
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-006y-9800000000-9ae37acdd6880d2b5b15
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-00dl-9500000000-04e4a14180f9ecbf261c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0903000000-ae545cd52cf21d62bac5
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01di-4900000000-3e4bea96ab1e4494a977
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01b9-9600000000-3422b818749cdac92bc1
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01b9-9400000000-9a807ba353a9d85f21a4
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01b9-9400000000-05e5ef5df3d0b69272ca
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01b9-9500000000-8ae951e802da41dc6224
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0901000000-44ac1cd2a68ec0f4bdfc
MS/MS Spectrum - , positiveLC-MS/MSsplash10-014i-0902000000-a4601550406e75607d7d

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Phenylalanine and derivatives
Alternative Parents
N-acyl-alpha amino acids / Phenylpropanoic acids / Monocyclic monoterpenoids / Menthane monoterpenoids / Aromatic monoterpenoids / Amphetamines and derivatives / Secondary carboxylic acid amides / Monocarboxylic acids and derivatives / Carboxylic acids / Organopnictogen compounds
show 4 more
Substituents
Phenylalanine or derivatives / N-acyl-alpha amino acid or derivatives / N-acyl-alpha-amino acid / 3-phenylpropanoic-acid / Amphetamine or derivatives / Aromatic monoterpenoid / P-menthane monoterpenoid / Monocyclic monoterpenoid / Monoterpenoid / Monocyclic benzene moiety
show 14 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
N-acyl-D-phenylalanine (CHEBI:31897)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sulfonylurea receptor activity
Specific Function
Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K(+) channels and insulin release.
Gene Name
ABCC8
Uniprot ID
Q09428
Uniprot Name
ATP-binding cassette sub-family C member 8
Molecular Weight
176990.36 Da
References
  1. Hu S, Wang S, Fanelli B, Bell PA, Dunning BE, Geisse S, Schmitz R, Boettcher BR: Pancreatic beta-cell K(ATP) channel activity and membrane-binding studies with nateglinide: A comparison with sulfonylureas and repaglinide. J Pharmacol Exp Ther. 2000 May;293(2):444-52. [PubMed:10773014]
  2. Sunaga Y, Gonoi T, Shibasaki T, Ichikawa K, Kusama H, Yano H, Seino S: 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. Eur J Pharmacol. 2001 Nov 9;431(1):119-25. [PubMed:11716850]
  3. Hansen AM, Christensen IT, Hansen JB, Carr RD, Ashcroft FM, Wahl P: Differential interactions of nateglinide and repaglinide on the human beta-cell sulphonylurea receptor 1. Diabetes. 2002 Sep;51(9):2789-95. [PubMed:12196472]
  4. Chachin M, Yamada M, Fujita A, Matsuoka T, Matsushita K, Kurachi Y: Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety, specifically inhibits pancreatic beta-cell-type K(ATP) channels. J Pharmacol Exp Ther. 2003 Mar;304(3):1025-32. [PubMed:12604678]
  5. Norman P, Rabasseda X: Nateglinide: A structurally novel, short-acting, hypoglycemic agent. Drugs Today (Barc). 2001 Jun;37(6):411-426. [PubMed:12764427]
  6. Dornhorst A: Insulinotropic meglitinide analogues. Lancet. 2001 Nov 17;358(9294):1709-16. [PubMed:11728565]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
References
  1. Scarsi M, Podvinec M, Roth A, Hug H, Kersten S, Albrecht H, Schwede T, Meyer UA, Rucker C: Sulfonylureas and glinides exhibit peroxisome proliferator-activated receptor gamma activity: a combined virtual screening and biological assay approach. Mol Pharmacol. 2007 Feb;71(2):398-406. Epub 2006 Nov 2. [PubMed:17082235]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Kirchheiner J, Meineke I, Muller G, Bauer S, Rohde W, Meisel C, Roots I, Brockmoller J: Influence of CYP2C9 and CYP2D6 polymorphisms on the pharmacokinetics of nateglinide in genotyped healthy volunteers. Clin Pharmacokinet. 2004;43(4):267-78. doi: 10.2165/00003088-200443040-00005. [PubMed:15005635]
  2. Takanohashi T, Kubo S, Nakayama A, Mihara R, Hayashi M: Inhibition of human liver microsomal CYP by nateglinide. J Pharm Pharmacol. 2010 May;62(5):592-7. doi: 10.1211/jpp.62.05.0005. [PubMed:20609060]
  3. Nateglinide FD label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Retinoic acid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Kirchheiner J, Meineke I, Muller G, Bauer S, Rohde W, Meisel C, Roots I, Brockmoller J: Influence of CYP2C9 and CYP2D6 polymorphisms on the pharmacokinetics of nateglinide in genotyped healthy volunteers. Clin Pharmacokinet. 2004;43(4):267-78. doi: 10.2165/00003088-200443040-00005. [PubMed:15005635]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Atpase activity, coupled to transmembrane movement of substances
Specific Function
May be an organic anion pump relevant to cellular detoxification.
Gene Name
ABCC4
Uniprot ID
O15439
Uniprot Name
Multidrug resistance-associated protein 4
Molecular Weight
149525.33 Da
References
  1. Uchida Y, Kamiie J, Ohtsuki S, Terasaki T: Multichannel liquid chromatography-tandem mass spectrometry cocktail method for comprehensive substrate characterization of multidrug resistance-associated protein 4 transporter. Pharm Res. 2007 Dec;24(12):2281-96. Epub 2007 Oct 16. [PubMed:17939016]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Symporter activity
Specific Function
Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucin...
Gene Name
SLC16A1
Uniprot ID
P53985
Uniprot Name
Monocarboxylate transporter 1
Molecular Weight
53943.685 Da
References
  1. Okamura A, Emoto A, Koyabu N, Ohtani H, Sawada Y: Transport and uptake of nateglinide in Caco-2 cells and its inhibitory effect on human monocarboxylate transporter MCT1. Br J Pharmacol. 2002 Oct;137(3):391-9. [PubMed:12237260]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Terada T, Sawada K, Saito H, Hashimoto Y, Inui K: Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2. Eur J Pharmacol. 2000 Mar 24;392(1-2):11-7. [PubMed:10748266]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Peptide:proton symporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name
SLC15A2
Uniprot ID
Q16348
Uniprot Name
Solute carrier family 15 member 2
Molecular Weight
81782.77 Da
References
  1. Terada T, Sawada K, Saito H, Hashimoto Y, Inui K: Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2. Eur J Pharmacol. 2000 Mar 24;392(1-2):11-7. [PubMed:10748266]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Uwai Y, Saito H, Hashimoto Y, Inui K: Inhibitory effect of anti-diabetic agents on rat organic anion transporter rOAT1. Eur J Pharmacol. 2000 Jun 16;398(2):193-7. [PubMed:10854830]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:49