Identification
- Generic Name
- Glisoxepide
- DrugBank Accession Number
- DB01289
- Background
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
Structure for Glisoxepide (DB01289)
- Weight
- Average: 449.524
Monoisotopic: 449.173289689 - Chemical Formula
- C20H27N5O5S
- Synonyms
- Glisoxepide
- 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.
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism AATP-sensitive inward rectifier potassium channel 8 inhibitorHumans UInsulin regulatorHumans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The metabolism of Glisoxepide can be increased when combined with Abatacept. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Glisoxepide. Acarbose The risk or severity of hypoglycemia can be increased when Acarbose is combined with Glisoxepide. Acebutolol The therapeutic efficacy of Glisoxepide can be increased when used in combination with Acebutolol. Aceclofenac The protein binding of Glisoxepide can be decreased when combined with Aceclofenac. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- 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
- Affected organisms
- 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
- 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. [Article]
- 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. [Article]
- External Links
- 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
Phase Status Purpose Conditions Count Not Available Completed Not Available Type 2 Diabetes Mellitus 3
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 189 °C PhysProp, U.S. Patent 3,668,215. - Predicted Properties
Property Value Source Water Solubility 0.103 mg/mL ALOGPS logP 1.57 ALOGPS logP 1.44 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 4.07 Chemaxon pKa (Strongest Basic) 1.59 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 133.64 Å2 Chemaxon Rotatable Bond Count 6 Chemaxon Refractivity 115.86 m3·mol-1 Chemaxon Polarizability 46.82 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9787 Blood Brain Barrier + 0.741 Caco-2 permeable - 0.6772 P-glycoprotein substrate Substrate 0.594 P-glycoprotein inhibitor I Non-inhibitor 0.7578 P-glycoprotein inhibitor II Non-inhibitor 0.9445 Renal organic cation transporter Non-inhibitor 0.8195 CYP450 2C9 substrate Substrate 0.5621 CYP450 2D6 substrate Non-substrate 0.8474 CYP450 3A4 substrate Non-substrate 0.6478 CYP450 1A2 substrate Non-inhibitor 0.9188 CYP450 2C9 inhibitor Non-inhibitor 0.6091 CYP450 2D6 inhibitor Non-inhibitor 0.848 CYP450 2C19 inhibitor Non-inhibitor 0.7913 CYP450 3A4 inhibitor Non-inhibitor 0.6763 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.7438 Ames test Non AMES toxic 0.7018 Carcinogenicity Non-carcinogens 0.7506 Biodegradation Ready biodegradable 0.5877 Rat acute toxicity 1.6845 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7225 hERG inhibition (predictor II) Non-inhibitor 0.6458
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-03du-9754100000-f939797a82a956924646 Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0udl-0254900000-62d5fd7aa30effeba4ba Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0002-0003900000-51226bb51ab27a0da24b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0fr6-2163900000-a9eb468bcc0c5e2d5761 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0536-6049400000-ce955597530d5e69fa0e Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00or-1491200000-7ddb0d4426f41c69e647 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-001l-9024100000-4e5d75f31f28b86a3c61 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 223.1341874 predictedDarkChem Lite v0.1.0 [M-H]- 235.9870874 predictedDarkChem Lite v0.1.0 [M-H]- 203.8095 predictedDeepCCS 1.0 (2019) [M+H]+ 224.8926874 predictedDarkChem Lite v0.1.0 [M+H]+ 236.8994874 predictedDarkChem Lite v0.1.0 [M+H]+ 206.16751 predictedDeepCCS 1.0 (2019) [M+Na]+ 223.4831874 predictedDarkChem Lite v0.1.0 [M+Na]+ 213.11467 predictedDeepCCS 1.0 (2019)
Targets
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- 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
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Regulator
- General Function
- Protease binding
- Specific Function
- Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen s...
- Gene Name
- INS
- Uniprot ID
- P01308
- Uniprot Name
- Insulin
- Molecular Weight
- 11980.795 Da
References
- Hausmann L, Schumann G, Kaffarnik H: [Insulin and pro-insulin secretion following intravenous administration of tolbutamide, glisoxepide and glibenclamide]. Arzneimittelforschung. 1978;28(1):83-6. [Article]
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
- 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. [Article]
Drug created at June 28, 2007 15:58 / Updated at June 24, 2022 21:18