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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2019-07-23 06:01:01 UTC
HMDB IDHMDB0015048
Secondary Accession Numbers
  • HMDB15048
Metabolite Identification
Common NameRepaglinide
DescriptionRepaglinide 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 cells of the pancreas to stimulate insulin release. Repaglinide 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 naive 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. Repaglinide is extensively metabolized in the liver and excreted in bile. Repaglinide metabolites do not possess appreciable hypoglycemic activity. Approximately 90% of a single orally administered dose is eliminated in feces and 8% in urine.
Structure
Data?1563861661
Synonyms
ValueSource
PrandinKegg
SurepostKegg
AG-ee 388 ZWHMDB
AG-ee 623 ZWHMDB
glaxo Wellcome brand OF replaginideMeSH
novo Nordisk brand 2 OF repaglinideMeSH
Repa-glinideMeSH
2-Ethoxy-4-(2-((3-methyl-1-(2-(1-piperidinyl)phenyl)butyl)amino)-2-oxoethyl)benzoic acidMeSH
novo Nordisk brand OF repaglinideMeSH
NovoNormMeSH
Repaglinide, (+-)-isomerMeSH
2-Ethoxy-N-(alpha-(2-methyl-1-propyl)-2-piperidinobenzyl)-4-carbamoylmethylbenzoic acidMeSH
AG-ee 388MeSH
GlucoNormMeSH
Chemical FormulaC27H36N2O4
Average Molecular Weight452.5857
Monoisotopic Molecular Weight452.26750765
IUPAC Name2-ethoxy-4-({[(1S)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butyl]carbamoyl}methyl)benzoic acid
Traditional Namerepaglinide
CAS Registry Number135062-02-1
SMILES
CCOC1=C(C=CC(CC(=O)N[C@@H](CC(C)C)C2=CC=CC=C2N2CCCCC2)=C1)C(O)=O
InChI Identifier
InChI=1S/C27H36N2O4/c1-4-33-25-17-20(12-13-22(25)27(31)32)18-26(30)28-23(16-19(2)3)21-10-6-7-11-24(21)29-14-8-5-9-15-29/h6-7,10-13,17,19,23H,4-5,8-9,14-16,18H2,1-3H3,(H,28,30)(H,31,32)/t23-/m0/s1
InChI KeyFAEKWTJYAYMJKF-QHCPKHFHSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPiperidines
Sub ClassPhenylpiperidines
Direct ParentPhenylpiperidines
Alternative Parents
Substituents
  • Phenylpiperidine
  • Phenylacetamide
  • Benzoic acid or derivatives
  • Benzoic acid
  • Phenoxy compound
  • Benzoyl
  • Phenol ether
  • Tertiary aliphatic/aromatic amine
  • Dialkylarylamine
  • Aniline or substituted anilines
  • Alkyl aryl ether
  • Benzenoid
  • Monocyclic benzene moiety
  • Amino acid
  • Tertiary amine
  • Carboxamide group
  • Amino acid or derivatives
  • Secondary carboxylic acid amide
  • Monocarboxylic acid or derivatives
  • Ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Azacycle
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Carbonyl group
  • Amine
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location:

Role

Industrial application:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point130 - 131 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0029 g/LNot Available
LogP5.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0029 g/LALOGPS
logP5.05ALOGPS
logP3.95ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)3.68ChemAxon
pKa (Strongest Basic)4.82ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area78.87 ŲChemAxon
Rotatable Bond Count10ChemAxon
Refractivity131.83 m³·mol⁻¹ChemAxon
Polarizability51.49 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0g7j-2958400000-8cbddf3d4598a0fc7340JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00ei-5260910000-4aaa7a93bda9f63c45e2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0udi-0000900000-c0108433e6c3f3bf1c75JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-004i-0009000000-30aa31031f07d8ae52b8JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-002r-0908000000-b76282b9697187110f0aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0000900000-2f6de321d96a7df0cde9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0udi-0140900000-4fef8b8042e88aa84955JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0290000000-4867f74dff429e78bb45JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0290000000-bdb018b622ca04e9d8b1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-001i-0590000000-60f613e4ee0d364efceaJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0f89-2791700000-333192fa8176a2febaa5JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0f6t-0181900000-f133163bc1e44e5ff6f3JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-1691100000-199236474a5fb7cb930dJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a5a-4940000000-4dc08f986e76785388e2JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0zfr-0010900000-dd8d5e58d8cda3e20087JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0bt9-1554900000-694c7b4171377cee14c4JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-2966000000-f2d3f7a4cbcb2910e30fJSpectraViewer | MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00912 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00912 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00912
Phenol Explorer Compound IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID59377
KEGG Compound IDC07670
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkRepaglinide
METLIN IDNot Available
PubChem Compound65981
PDB IDNot Available
ChEBI ID348669
Food Biomarker OntologyNot Available
VMH IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Massi-Benedetti M, Damsbo P: Pharmacology and clinical experience with repaglinide. Expert Opin Investig Drugs. 2000 Apr;9(4):885-98. [PubMed:11060717 ]

Enzymes

General function:
Involved in monooxygenase 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 xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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. Bidstrup TB, Bjornsdottir I, Sidelmann UG, Thomsen MS, Hansen KT: CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide. Br J Clin Pharmacol. 2003 Sep;56(3):305-14. [PubMed:12919179 ]
General function:
Involved in monooxygenase 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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids. It is the principal enzyme responsible for the metabolism the anti-cancer drug paclitaxel (taxol).
Gene Name:
CYP2C8
Uniprot ID:
P10632
Molecular weight:
55824.275
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. Bidstrup TB, Bjornsdottir I, Sidelmann UG, Thomsen MS, Hansen KT: CYP2C8 and CYP3A4 are the principal enzymes involved in the human in vitro biotransformation of the insulin secretagogue repaglinide. Br J Clin Pharmacol. 2003 Sep;56(3):305-14. [PubMed:12919179 ]
General function:
Involved in DNA binding
Specific function:
Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular weight:
57619.6
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 ]
General function:
Involved in ATP binding
Specific function:
Putative 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:
177006.4
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. Wangler B, Schneider S, Thews O, Schirrmacher E, Comagic S, Feilen P, Schwanstecher C, Schwanstecher M, Shiue CY, Alavi A, Hohnemann S, Piel M, Rosch F, Schirrmacher R: Synthesis and evaluation of (S)-2-(2-[18F]fluoroethoxy)-4-([3-methyl-1-(2-piperidin-1-yl-phenyl)-butyl-carbam oyl]-methyl)-benzoic acid ([18F]repaglinide): a promising radioligand for quantification of pancreatic beta-cell mass with positron emission tomography (PET). Nucl Med Biol. 2004 Jul;31(5):639-47. [PubMed:15219283 ]
  5. Wangler B, Beck C, Shiue CY, Schneider S, Schwanstecher C, Schwanstecher M, Feilen PJ, Alavi A, Rosch F, Schirrmacher R: Synthesis and in vitro evaluation of (S)-2-([11C]methoxy)-4-[3-methyl-1-(2-piperidine-1-yl-phenyl)-butyl-carbamoyl]-be nzoic acid ([11C]methoxy-repaglinide): a potential beta-cell imaging agent. Bioorg Med Chem Lett. 2004 Oct 18;14(20):5205-9. [PubMed:15380228 ]
  6. Dornhorst A: Insulinotropic meglitinide analogues. Lancet. 2001 Nov 17;358(9294):1709-16. [PubMed:11728565 ]