Identification

Name
Glisoxepide
Accession Number
DB01289
Description

Glisoxepide is one of the sulphonamide-derived oral antidiabetic drugs. It inhibits the uptake of bile acids into isolated rat hepatocytes. However it inhibits taurocholate uptake only in the absence of sodium ions. Glisoxepide uptake could be further inhibited by blockers of the hepatocellular monocarboxylate transporter, by the loop diuretic bumetanide, by 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) and by sulphate. These results are consistent with the transport of glisoxepide via the transport system for the unconjugated bile acid cholate. 1,2

Type
Small Molecule
Groups
Investigational
Structure
Thumb
Weight
Average: 449.524
Monoisotopic: 449.173289689
Chemical Formula
C20H27N5O5S
Synonyms
Not Available
External IDs
  • BAY B 4231
  • BAY-B-4231
  • FBB 4231
  • FBB-4231
  • RP 22410
  • RP-22410

Pharmacology

Indication

For the treatment of diabetes mellitus type 2.

Contraindications & Blackbox Warnings
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Pharmacodynamics

Glisoxepide is a sulfonylurea agent. It stimulates beta cells of the islet of Langerhans in the pancreas to release insulin. It also enhances peripheral insulin sensitivity. Overall it potentiates insulin release and improves insulin dynamics.

Mechanism of action

Glisoxepide is a hypoglycemic sulphonylurea agent. The sulphonylureas are a family of drugs based on a common sulphonylurea core. These drugs act via augmentation of secretion of insulin from pancreatic beta-cells. Sulphonylureas may also cause a reduction in serum glucagon and potentiate the action of insulin at the extrapancreatic tissues. Glisoxepide functions as a non-selective K(ATP) channel blocker. It is thought to stimulate insulin secretion by closing the ATP-sensitive K(+) (K(ATP)) channels (Kir6.2/SUR1 complex, KATP channels) in pancreatic beta-cells. This inhibits a tonic, hyperpolarizing efflux of potassium, thus causing the electric potential over the membrane to become more positive. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.

TargetActionsOrganism
AATP-sensitive inward rectifier potassium channel 8
inhibitor
Humans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half-life
Not Available
Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbaloparatideThe therapeutic efficacy of Glisoxepide can be decreased when used in combination with Abaloparatide.
AbataceptThe metabolism of Glisoxepide can be increased when combined with Abatacept.
AbirateroneThe metabolism of Glisoxepide can be decreased when combined with Abiraterone.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Glisoxepide.
AcebutololThe therapeutic efficacy of Glisoxepide can be increased when used in combination with Acebutolol.
AceclofenacThe protein binding of Glisoxepide can be decreased when combined with Aceclofenac.
AcemetacinThe protein binding of Glisoxepide can be decreased when combined with Acemetacin.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Glisoxepide.
AcetazolamideThe therapeutic efficacy of Glisoxepide can be increased when used in combination with Acetazolamide.
AcetohexamideThe risk or severity of hypoglycemia can be increased when Acetohexamide is combined with Glisoxepide.
Additional Data Available
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  • Severity
    Severity
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    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
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    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
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Food Interactions
Not Available

Products

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International/Other Brands
Glucoben (Farmades) / Glysepin (Bayer) / Pro-Diaban (Bayer)

Categories

ATC Codes
A10BB11 — Glisoxepide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzenesulfonamides
Direct Parent
Benzenesulfonamides
Alternative Parents
Benzenesulfonyl compounds / 2-heteroaryl carboxamides / Sulfonylureas / Azepanes / Semicarbazides / Aminosulfonyl compounds / Heteroaromatic compounds / Isoxazoles / Organosulfonic acids and derivatives / Secondary carboxylic acid amides
show 7 more
Substituents
2-heteroaryl carboxamide / Aminosulfonyl compound / Aromatic heteromonocyclic compound / Azacycle / Azepane / Azole / Benzenesulfonamide / Benzenesulfonyl group / Carbonic acid derivative / Carbonyl group
show 20 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
H7SC0I332I
CAS number
25046-79-1
InChI Key
ZKUDBRCEOBOWLF-UHFFFAOYSA-N
InChI
InChI=1S/C20H27N5O5S/c1-15-14-18(23-30-15)19(26)21-11-10-16-6-8-17(9-7-16)31(28,29)24-20(27)22-25-12-4-2-3-5-13-25/h6-9,14H,2-5,10-13H2,1H3,(H,21,26)(H2,22,24,27)
IUPAC Name
N-{2-[4-({[(azepan-1-yl)carbamoyl]amino}sulfonyl)phenyl]ethyl}-5-methyl-1,2-oxazole-3-carboxamide
SMILES
CC1=CC(=NO1)C(=O)NCCC1=CC=C(C=C1)S(=O)(=O)NC(=O)NN1CCCCCC1

References

Synthesis Reference

U.S. Patent 3,668,215.

General References
  1. Fuckel D, Petzinger E: Interaction of sulfonylureas with the transport of bile acids into hepatocytes. Eur J Pharmacol. 1992 Mar 31;213(3):393-404. [PubMed:1618280]
  2. Selvaag E: Photohemolytic potency of oral antidiabetic drugs in vitro: effects of antioxidants and a nitrogen atmosphere. Photodermatol Photoimmunol Photomed. 1996 Aug;12(4):166-70. [PubMed:9017793]
Human Metabolome Database
HMDB0015406
PubChem Compound
32778
PubChem Substance
46508780
ChemSpider
30380
ChEBI
135731
ChEMBL
CHEMBL2106618
ZINC
ZINC000000537804
Therapeutic Targets Database
DAP000925
PharmGKB
PA164743233
Wikipedia
Glisoxepide

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus3

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)189 °CPhysProp, U.S. Patent 3,668,215.
Predicted Properties
PropertyValueSource
Water Solubility0.103 mg/mLALOGPS
logP1.57ALOGPS
logP1.44ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)4.07ChemAxon
pKa (Strongest Basic)1.59ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area133.64 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity115.86 m3·mol-1ChemAxon
Polarizability46.83 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9787
Blood Brain Barrier+0.741
Caco-2 permeable-0.6772
P-glycoprotein substrateSubstrate0.594
P-glycoprotein inhibitor INon-inhibitor0.7578
P-glycoprotein inhibitor IINon-inhibitor0.9445
Renal organic cation transporterNon-inhibitor0.8195
CYP450 2C9 substrateSubstrate0.5621
CYP450 2D6 substrateNon-substrate0.8474
CYP450 3A4 substrateNon-substrate0.6478
CYP450 1A2 substrateNon-inhibitor0.9188
CYP450 2C9 inhibitorNon-inhibitor0.6091
CYP450 2D6 inhibitorNon-inhibitor0.848
CYP450 2C19 inhibitorNon-inhibitor0.7913
CYP450 3A4 inhibitorNon-inhibitor0.6763
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7438
Ames testNon AMES toxic0.7018
CarcinogenicityNon-carcinogens0.7506
BiodegradationReady biodegradable0.5877
Rat acute toxicity1.6845 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7225
hERG inhibition (predictor II)Non-inhibitor0.6458
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

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Inward rectifier potassium channel activity
Specific Function
This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their...
Gene Name
KCNJ8
Uniprot ID
Q15842
Uniprot Name
ATP-sensitive inward rectifier potassium channel 8
Molecular Weight
47967.455 Da
References
  1. Szewczyk A, Wojcik G, Lobanov NA, Nalecz MJ: The mitochondrial sulfonylurea receptor: identification and characterization. Biochem Biophys Res Commun. 1997 Jan 23;230(3):611-5. [PubMed:9015372]
  2. Sato T, Costa AD, Saito T, Ogura T, Ishida H, Garlid KD, Nakaya H: Bepridil, an antiarrhythmic drug, opens mitochondrial KATP channels, blocks sarcolemmal KATP channels, and confers cardioprotection. J Pharmacol Exp Ther. 2006 Jan;316(1):182-8. Epub 2005 Sep 20. [PubMed:16174795]

Enzymes

Kind
Protein
Organism
Humans
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. May M, Schindler C: Clinically and pharmacologically relevant interactions of antidiabetic drugs. Ther Adv Endocrinol Metab. 2016 Apr;7(2):69-83. doi: 10.1177/2042018816638050. Epub 2016 Mar 31. [PubMed:27092232]

Drug created on June 28, 2007 09:58 / Updated on June 12, 2020 10:51

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