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Identification
NameNateglinide
Accession NumberDB00731  (APRD00593)
TypeSmall Molecule
GroupsApproved, 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
SynonymsNot Available
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Starlixtablet60 mg/1oralNovartis Pharmaceuticals Corporation2000-12-04Not applicableUs
Starlixtablet120 mg/1oralNovartis Pharmaceuticals Corporation2000-12-04Not applicableUs
Starlix 120mgtablet120 mgoralNovartis Pharmaceuticals Canada Inc2002-03-052015-07-13Canada
Starlix 180mgtablet180 mgoralNovartis Pharmaceuticals Canada Inc2002-03-052009-02-19Canada
Starlix 60mgtablet60 mgoralNovartis Pharmaceuticals Canada Inc2002-03-052015-07-13Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Nateglinidetablet120 mg/1oralDr. Reddy's Laboratories Limited2009-09-09Not applicableUs
Nateglinidetablet60 mg/1oralWatson Laboratories, Inc.2011-03-30Not applicableUs
Nateglinidetablet60 mg/1oralDr. Reddy's Laboratories Limited2009-09-09Not applicableUs
Nateglinidetablet, coated120 mg/1oralAv Kare, Inc.2016-04-06Not applicableUs
Nateglinidetablet, coated120 mg/1oralPhysicians Total Care, Inc.2011-05-03Not applicableUs
Nateglinidetablet, coated60 mg/1oralAv Kare, Inc.2016-04-06Not applicableUs
Nateglinidetablet, coated120 mg/1oralPar Pharmaceutical Inc.2009-09-08Not applicableUs
Nateglinidetablet, coated120 mg/1oralAmerican Health Packaging2011-01-18Not applicableUs
Nateglinidetablet, coated60 mg/1oralPar Pharmaceutical Inc.2009-09-08Not applicableUs
Nateglinidetablet, coated60 mg/1oralAmerican Health Packaging2011-01-18Not applicableUs
Nateglinidetablet, coated120 mg/1oralNcs Health Care Of Ky, Inc Dba Vangard Labs2009-09-08Not applicableUs
Nateglinidetablet, coated120 mg/1oralGolden State Medical Supply, Inc.2015-09-10Not applicableUs
Nateglinidetablet, coated60 mg/1oralNcs Health Care Of Ky, Inc Dba Vangard Labs2009-09-08Not applicableUs
Nateglinidetablet, coated60 mg/1oralGolden State Medical Supply, Inc.2015-09-10Not applicableUs
Nateglinidetablet120 mg/1oralWatson Laboratories, Inc.2011-03-30Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
FasticNot Available
StarsisNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
SDZ-DJN 608
ThumbNot applicableDBSALT000922
Categories
UNII41X3PWK4O2
CAS number105816-04-4
WeightAverage: 317.4226
Monoisotopic: 317.199093735
Chemical FormulaC19H27NO3
InChI KeyInChIKey=OELFLUMRDSZNSF-YJEKIOLLSA-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)-3-phenyl-2-{[4-(propan-2-yl)cyclohexyl]formamido}propanoic acid
SMILES
CC(C)C1CC[C@@H](CC1)C(=O)N[[email protected]](CC1=CC=CC=C1)C(O)=O
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as n-acyl-aliphatic-alpha amino acids. These are alpha amino acids carrying a N-acylated aliphatic chain.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentN-acyl-aliphatic-alpha amino acids
Alternative Parents
Substituents
  • N-acyl-aliphatic-alpha amino acid
  • 3-phenylpropanoic-acid
  • Menthane monoterpenoid
  • Monoterpenoid
  • Monocyclic monoterpenoid
  • Aromatic monoterpenoid
  • Amphetamine or derivatives
  • Amino fatty acid
  • Fatty acyl
  • Benzenoid
  • Monocyclic benzene moiety
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the treatment of non-insulin dependent-diabetes mellitus in conjunction with diet and exercise.
PharmacodynamicsInsulin 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 actionNateglinide 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.
Related Articles
AbsorptionRapidly 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 binding98% 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.

SubstrateEnzymesProduct
Nateglinide
Nateglinide metabolite M2/M3Details
Nateglinide metabolite M2/M3
Not Available
Nateglinide metabolite M11/M12Details
Nateglinide
Nateglinide metabolite M1Details
Nateglinide metabolite M1
Not Available
Nateglinide metabolite M11/M12Details
Nateglinide
Not Available
Nateglinide metabolite M7Details
Nateglinide metabolite M7
Not Available
Nateglinide metabolite M11/M12Details
Nateglinide
Nateglinide glucuronide and isomers (M4/M5/M6)Details
Route of eliminationUrine (83%) and feces (10%)
Half life1.5 hours
ClearanceNot Available
ToxicityAn overdose may result in an exaggerated glucose-lowering effect with the development of hypoglycemic symptoms.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Nateglinide Action PathwayDrug actionSMP00453
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Dr reddys laboratories ltd
  • Par pharmaceutical inc
  • Teva pharmaceuticals usa
  • Novartis pharmaceuticals corp
Packagers
Dosage forms
FormRouteStrength
Tablet, coatedoral120 mg/1
Tablet, coatedoral60 mg/1
Tabletoral120 mg/1
Tabletoral60 mg/1
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)
CA2114678 No1999-04-272014-02-01Canada
CA2271865 No2003-10-142017-11-14Canada
US6559188 No2000-09-152020-09-15Us
US6641841 No1997-11-142017-11-14Us
US6844008 No1997-11-142017-11-14Us
US6878749 No2000-09-152020-09-15Us
USRE34878 No1992-09-082009-09-08Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilityPractically insolubleNot Available
logP2.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00848 mg/mLALOGPS
logP3.59ALOGPS
logP4.03ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)4ChemAxon
pKa (Strongest Basic)-0.38ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area66.4 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity89.46 m3·mol-1ChemAxon
Polarizability35.57 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

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

US20030229249
General ReferencesNot Available
External Links
ATC CodesA10BX03
AHFS Codes
  • 68:20.16
PDB EntriesNot Available
FDA labelDownload (56.5 KB)
MSDSNot Available
Interactions
Drug Interactions
Drug
AcetohexamideAcetohexamide may increase the hypoglycemic activities of Nateglinide.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Nateglinide.
AlogliptinAlogliptin may increase the hypoglycemic activities of Nateglinide.
BexaroteneThe serum concentration of Nateglinide can be decreased when it is combined with Bexarotene.
BosentanThe serum concentration of Nateglinide can be decreased when it is combined with Bosentan.
CanagliflozinCanagliflozin may increase the hypoglycemic activities of Nateglinide.
ChlorpropamideChlorpropamide may increase the hypoglycemic activities of Nateglinide.
ConivaptanThe serum concentration of Nateglinide can be increased when it is combined with Conivaptan.
DabrafenibThe serum concentration of Nateglinide can be decreased when it is combined with Dabrafenib.
DasatinibThe serum concentration of Nateglinide can be increased when it is combined with Dasatinib.
DeferasiroxThe serum concentration of Nateglinide can be decreased when it is combined with Deferasirox.
DihydrotestosteroneDihydrotestosterone may increase the hypoglycemic activities of Nateglinide.
EltrombopagThe serum concentration of Nateglinide can be increased when it is combined with Eltrombopag.
FloxuridineThe metabolism of Nateglinide can be decreased when combined with Floxuridine.
FluconazoleThe metabolism of Nateglinide can be decreased when combined with Fluconazole.
FosaprepitantThe serum concentration of Nateglinide can be increased when it is combined with Fosaprepitant.
Fusidic AcidThe serum concentration of Nateglinide can be increased when it is combined with Fusidic Acid.
GliclazideGliclazide may increase the hypoglycemic activities of Nateglinide.
GlimepirideGlimepiride may increase the hypoglycemic activities of Nateglinide.
GliquidoneGliquidone may increase the hypoglycemic activities of Nateglinide.
GlyburideGlyburide may increase the hypoglycemic activities of Nateglinide.
IdelalisibThe serum concentration of Nateglinide can be increased when it is combined with Idelalisib.
Insulin AspartInsulin Aspart may increase the hypoglycemic activities of Nateglinide.
Insulin DetemirInsulin Detemir may increase the hypoglycemic activities of Nateglinide.
Insulin GlargineInsulin Glargine may increase the hypoglycemic activities of Nateglinide.
Insulin GlulisineInsulin Glulisine may increase the hypoglycemic activities of Nateglinide.
Insulin HumanInsulin Regular may increase the hypoglycemic activities of Nateglinide.
Insulin LisproInsulin Lispro may increase the hypoglycemic activities of Nateglinide.
IvacaftorThe serum concentration of Nateglinide can be increased when it is combined with Ivacaftor.
LeuprolideThe therapeutic efficacy of Nateglinide can be decreased when used in combination with Leuprolide.
LinagliptinLinagliptin may increase the hypoglycemic activities of Nateglinide.
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Nateglinide.
LuliconazoleThe serum concentration of Nateglinide can be increased when it is combined with Luliconazole.
MetforminMetformin may increase the hypoglycemic activities of Nateglinide.
MifepristoneThe serum concentration of Nateglinide can be increased when it is combined with Mifepristone.
MitotaneThe serum concentration of Nateglinide can be decreased when it is combined with Mitotane.
NelfinavirThe metabolism of Nateglinide can be decreased when combined with Nelfinavir.
NetupitantThe serum concentration of Nateglinide can be increased when it is combined with Netupitant.
OxandroloneOxandrolone may increase the hypoglycemic activities of Nateglinide.
PalbociclibThe serum concentration of Nateglinide can be increased when it is combined with Palbociclib.
ParoxetineParoxetine may increase the hypoglycemic activities of Nateglinide.
PegvisomantPegvisomant may increase the hypoglycemic activities of Nateglinide.
PhenelzinePhenelzine may increase the hypoglycemic activities of Nateglinide.
PhenytoinThe metabolism of Nateglinide can be increased when combined with Phenytoin.
RepaglinideRepaglinide may increase the hypoglycemic activities of Nateglinide.
SaxagliptinSaxagliptin may increase the hypoglycemic activities of Nateglinide.
SecobarbitalThe metabolism of Nateglinide can be increased when combined with Secobarbital.
SiltuximabThe serum concentration of Nateglinide can be decreased when it is combined with Siltuximab.
SimeprevirThe serum concentration of Nateglinide can be increased when it is combined with Simeprevir.
SparfloxacinSparfloxacin may increase the hypoglycemic activities of Nateglinide.
St. John's WortThe serum concentration of Nateglinide can be decreased when it is combined with St. John&#39;s Wort.
StiripentolThe serum concentration of Nateglinide can be increased when it is combined with Stiripentol.
SulfisoxazoleThe metabolism of Nateglinide can be decreased when combined with Sulfisoxazole.
TeriflunomideThe serum concentration of Nateglinide can be increased when it is combined with Teriflunomide.
TestosteroneTestosterone may increase the hypoglycemic activities of Nateglinide.
TocilizumabThe serum concentration of Nateglinide can be decreased when it is combined with Tocilizumab.
TolbutamideTolbutamide may increase the hypoglycemic activities of Nateglinide.
TranylcypromineTranylcypromine may increase the hypoglycemic activities of Nateglinide.
TrichlormethiazideThe therapeutic efficacy of Nateglinide can be decreased when used in combination with Trichlormethiazide.
VildagliptinVildagliptin may increase the hypoglycemic activities of Nateglinide.
Food Interactions
  • Take upto 30 minutes before meals.

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
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) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation...
Gene Name:
PPARG
Uniprot ID:
P37231
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 unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 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:
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
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 unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A7
Uniprot ID:
P24462
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 gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the gener...
Gene Name:
PTGS1
Uniprot ID:
P23219
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 transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A9
Uniprot ID:
O60656
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 antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
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 ]

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 colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Molecular Weight:
69365.94 Da
References
  1. Novartis. Starlix® (nateglinide) tablets prescribing information. East Hanover, NJ; 2009 Nov.
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 the body. Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Gene Name:
ORM1
Uniprot ID:
P02763
Molecular Weight:
23511.38 Da
References
  1. Novartis. Starlix® (nateglinide) tablets prescribing information. East Hanover, NJ; 2009 Nov.

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
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 leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. Depending on the tissue and on cicumstances, mediates the import or export of lactic acid and ketone bod...
Gene Name:
SLC16A1
Uniprot ID:
P53985
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
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
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 molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
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 ]
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Drug created on June 13, 2005 07:24 / Updated on May 27, 2016 02:17