Tmic
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Record Information
Version2.0
Creation Date2009-07-03 22:08:18 UTC
Update Date2014-12-24 20:25:35 UTC
Accession NumberT3D2483
Identification
Common NameGlipizide
ClassSmall Molecule
DescriptionGlipizide is only found in individuals that have used or taken this drug. It is an oral hypoglycemic agent which is rapidly absorbed and completely metabolized. [PubChem]Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.
Compound Type
  • Amide
  • Amine
  • Drug
  • Hypoglycemic Agent
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1-Cyclohexyl-3-({p-[2-(5-methylpyrazinecarboxamido)ethyl]phenyl}sulfonyl)urea
Aldiab
CP 28,720
CP 28720
CP-28,720
Digrin
Dipazide
Glibenese
Glibetin
Glican
Glidiab
Glipid
Glipin
Glipizida
GlipizideER
Glipizidum
Glix
Gluco-rite
Glucolip
Glucotrol
Glucotrol XL
Glucozide
Glupitel
Glupizide
Glyde
Glydiazinamide
K 4024
Melizide
Mindiab
Minidab
Minidiab
Minodiab
N-{4-[beta-(5-methylpyrazine-2-carboxamido)ethyl]benzenesulphonyl}-n'-cyclohexylurea
Napizide
Ozidia
Sucrazide
Zitrol XR
Chemical FormulaC21H27N5O4S
Average Molecular Mass445.535 g/mol
Monoisotopic Mass445.178 g/mol
CAS Registry Number29094-61-9
IUPAC NameN-[2-(4-{[(cyclohexylcarbamoyl)amino]sulfonyl}phenyl)ethyl]-5-methylpyrazine-2-carboxamide
Traditional Nameglipizide
SMILESCC1=CN=C(C=N1)C(O)=NCCC1=CC=C(C=C1)S(=O)(=O)NC(O)=NC1CCCCC1
InChI IdentifierInChI=1S/C21H27N5O4S/c1-15-13-24-19(14-23-15)20(27)22-12-11-16-7-9-18(10-8-16)31(29,30)26-21(28)25-17-5-3-2-4-6-17/h7-10,13-14,17H,2-6,11-12H2,1H3,(H,22,27)(H2,25,26,28)
InChI KeyInChIKey=ZJJXGWJIGJFDTL-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzenesulfonamides. These are organic compounds containing a sulfonamide group that is S-linked to a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzenesulfonamides
Direct ParentBenzenesulfonamides
Alternative Parents
Substituents
  • Benzenesulfonamide
  • Benzenesulfonyl group
  • Sulfonylurea
  • Pyrazine
  • Organic sulfonic acid or derivatives
  • Heteroaromatic compound
  • Aminosulfonyl compound
  • Sulfonyl
  • Organosulfonic acid or derivatives
  • Carboximidic acid
  • Carboximidic acid derivative
  • Azacycle
  • Organoheterocyclic compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point200-203°C
Boiling PointNot Available
Solubility37.2 mg/L
LogP1.91
Predicted Properties
PropertyValueSource
Water Solubility0.016 g/LALOGPS
logP1.83ALOGPS
logP1.43ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)4.32ChemAxon
pKa (Strongest Basic)0.059ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area130.15 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity115.62 m³·mol⁻¹ChemAxon
Polarizability47.64 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udj-9433200000-0daa174c6f208f739d92View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-014i-0119600000-895a0f8ef34678f1200dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-014i-0009600000-3a2ab7e8e725ab4b2090View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0v4i-3941000000-57ab7532afaad5f9a2acView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014i-0009600000-3a2ab7e8e725ab4b2090View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-0329000000-a6f7044e9dfe397cfcddView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014i-0119600000-895a0f8ef34678f1200dView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-1429000000-60bdb648d5355af7a75bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0v4i-3941000000-57ab7532afaad5f9a2acView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-006t-1209300000-c14d0f75f56599ec527fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-7903000000-63e0326a933897ad8d58View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05mk-9700000000-3dea1f33244b9e19e407View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0007-5208900000-36b94e0ee176fc17450fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00kb-4529000000-18be67f87a3195a21fffView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0007-9310000000-3bae0e1f24a4fc985c6bView in MoNA
Toxicity Profile
Route of ExposureOral. Gastrointestinal absorption is uniform, rapid, and essentially complete.
Mechanism of ToxicitySulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.
MetabolismHepatic. The major metabolites of glipizide are products of aromatic hydroxylation and have no hypoglycemic activity. A minor metabolite which accounts for less than 2% of a dose, an acetylaminoethyl benzine derivatives, is reported to have 1/10 to 1/3 as much hypoglycemic activity as the parent compound. Route of Elimination: The primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine. Half Life: 2-5 hours
Toxicity ValuesThe acute oral toxicity was extremely low in all species tested (LD50 greater than 4 g/kg).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor use as an adjunct to diet for the control of hyperglycemia and its associated symptomatology in patients with non-insulin-dependent diabetes mellitus (NIDDM; type II), formerly known as maturity-onset diabetes, after an adequate trial of dietary therapy has proved unsatisfactory.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsThe acute oral toxicity was extremely low in all species tested (LD50 greater than 4 g/kg). Overdosage of sulfonylureas including glipizide can produce hypoglycemia.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01067
HMDB IDHMDB15200
PubChem Compound ID3478
ChEMBL IDCHEMBL1073
ChemSpider ID3359
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID239286
BioCyc IDNot Available
CTD IDD005913
Stitch IDGlipizide
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkGlipizide
References
Synthesis Reference

Suresh Kumar Gidwani, Purushottam Singnurkar, Prashant Kumar Tewari, “Sustained release pharmaceutical composition containing glipizide and method for producing same.” U.S. Patent US6270797, issued February, 2000.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Wikipedia. Glipizide. Last Updated 15 May 2009. [Link]
  3. Drugs.com [Link]
  4. RxList: The Internet Drug Index (2009). [Link]
  5. MedTV (2009). Glipizide Overdose. [Link]
  6. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

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. Gribble FM, Ashcroft FM: Sulfonylurea sensitivity of adenosine triphosphate-sensitive potassium channels from beta cells and extrapancreatic tissues. Metabolism. 2000 Oct;49(10 Suppl 2):3-6. [11078468 ]
  2. Harrower A: Gliclazide modified release: from once-daily administration to 24-hour blood glucose control. Metabolism. 2000 Oct;49(10 Suppl 2):7-11. [11078469 ]
  3. Lawrence CL, Proks P, Rodrigo GC, Jones P, Hayabuchi Y, Standen NB, Ashcroft FM: Gliclazide produces high-affinity block of KATP channels in mouse isolated pancreatic beta cells but not rat heart or arterial smooth muscle cells. Diabetologia. 2001 Aug;44(8):1019-25. [11484080 ]
  4. Reimann F, Ashcroft FM, Gribble FM: Structural basis for the interference between nicorandil and sulfonylurea action. Diabetes. 2001 Oct;50(10):2253-9. [11574406 ]
  5. Proks P, Reimann F, Green N, Gribble F, Ashcroft F: Sulfonylurea stimulation of insulin secretion. Diabetes. 2002 Dec;51 Suppl 3:S368-76. [12475777 ]
General Function:
Phosphatidylinositol-4,5-bisphosphate binding
Specific Function:
In the kidney, probably plays a major role in potassium homeostasis. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This channel is activated by internal ATP and can be blocked by external barium.
Gene Name:
KCNJ1
Uniprot ID:
P48048
Molecular Weight:
44794.6 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
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 and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
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. [17082235 ]