DT-Web

DB01382 - Glycodiazine


Identification
Name Glycodiazine
Accession Number DB01382
Type small molecule
Description Glycodiazine is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin. The mechanism of action of glycodiazine in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glycodiazine likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. This increase in intracellular calcium ion concentration induces the secretion of insulin. It is used for the concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 309.341
Groups approved
Monoisotopic Weight 309.078326673
Pharmacology
Indication Glycodiazine is used concomitantly with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.
Mechanism of action The mechanism of action of glycodiazine in lowering blood glucose appears to be dependent on stimulating the release of insulin from functioning pancreatic beta cells, and increasing sensitivity of peripheral tissues to insulin. Glycodiazine likely binds to ATP-sensitive potassium channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Membrane depolarization stimulates calcium ion influx through voltage-sensitive calcium channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin.
Absorption Rapidly and completely absorbed following oral administration.
Protein binding 90% bound to plasma proteins.
Biotransformation Not Available
Route of elimination Not Available
Toxicity Severe hypoglycemic reactions with coma, seizure, or other neurological impairment.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Acetylsalicylic acid Acetylsalicylic acid increases the effect of sulfonylurea, glycodiazine.
Atenolol The beta-blocker, atenolol, may decrease symptoms of hypoglycemia.
Bisoprolol The beta-blocker, bisoprolol, may decrease symptoms of hypoglycemia.
Carvedilol The beta-blocker, carvedilol, may decrease symptoms of hypoglycemia.
Chloramphenicol Chloramphenicol may increase the effect of sulfonylurea, glycodiazine.
Clofibrate Clofibrate may increase the effect of sulfonylurea, glycodiazine.
Esmolol The beta-blocker, esmolol, may decrease symptoms of hypoglycemia.
Labetalol The beta-blocker, labetalol, may decrease symptoms of hypoglycemia.
Metoprolol The beta-blocker, metoprolol, may decrease symptoms of hypoglycemia.
Nadolol The beta-blocker, nadolol, may decrease symptoms of hypoglycemia.
Oxprenolol The beta-blocker, oxprenolol, may decrease symptoms of hypoglycemia.
Phenylbutazone Phenylbutazone increases the effect of the hypoglycemic agent
Pindolol The beta-blocker, pindolol, may decrease symptoms of hypoglycemia.
Propranolol The beta-blocker, propranolol, may decrease symptoms of hypoglycemia.
Rifampin Rifampin may decrease the effect of sulfonylurea, glycodiazine.
Timolol The beta-blocker, timolol, may decrease symptoms of hypoglycemia.
Food Interactions Not Available

Targets


ATP-sensitive inward rectifier potassium channel 1
Name ATP-sensitive inward rectifier potassium channel 1
Gene Name KCNJ1
Pharmacological action yes
Actions other/unknown
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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. - Pubmed
  • Guirgis FK, Ghanem MH, Abdel-Hay MM: Comparative study of the hypoglycaemic and antilipolytic effects of four antidiabetic agents administered i.v. Arzneimittelforschung. 1976;26(3):435-7. - Pubmed
  • Greeley SA, Tucker SE, Naylor RN, Bell GI, Philipson LH: Neonatal diabetes mellitus: A model for personalized medicine. Trends Endocrinol Metab. 2010 Apr 28. - Pubmed
  • Pondugula SR, Raveendran NN, Ergonul Z, Deng Y, Chen J, Sanneman JD, Palmer LG, Marcus DC: Glucocorticoid regulation of genes in the amiloride-sensitive sodium transport pathway by semicircular canal duct epithelium of neonatal rat. Physiol Genomics. 2006 Jan 12;24(2):114-23. Epub 2005 Nov 1. - Pubmed
  • Lu M, Leng Q, Egan ME, Caplan MJ, Boulpaep EL, Giebisch GH, Hebert SC: CFTR is required for PKA-regulated ATP sensitivity of Kir1.1 potassium channels in mouse kidney. J Clin Invest. 2006 Mar;116(3):797-807. Epub 2006 Feb 9. - Pubmed
  • Serrano-Martin X, Payares G, Mendoza-Leon A: Glibenclamide, a blocker of K+(ATP) channels, shows antileishmanial activity in experimental murine cutaneous leishmaniasis. Antimicrob Agents Chemother. 2006 Dec;50(12):4214-6. Epub 2006 Oct 2. - Pubmed
DTHybrid score 0.6447
ATP-binding cassette transporter sub-family C member 8
Name ATP-binding cassette transporter sub-family C member 8
Gene Name ABCC8
Pharmacological action unknown
Actions inducer
References
  • Dabrowski M, Ashcroft FM, Ashfield R, Lebrun P, Pirotte B, Egebjerg J, Bondo Hansen J, Wahl P: The novel diazoxide analog 3-isopropylamino-7-methoxy-4H-1,2,4-benzothiadiazine 1,1-dioxide is a selective Kir6.2/SUR1 channel opener. Diabetes. 2002 Jun;51(6):1896-906. - Pubmed
  • Hambrock A, Preisig-Muller R, Russ U, Piehl A, Hanley PJ, Ray J, Daut J, Quast U, Derst C: Four novel splice variants of sulfonylurea receptor 1. Am J Physiol Cell Physiol. 2002 Aug;283(2):C587-98. - Pubmed
  • Hambrock A, Loffler-Walz C, Quast U: Glibenclamide binding to sulphonylurea receptor subtypes: dependence on adenine nucleotides. Br J Pharmacol. 2002 Aug;136(7):995-1004. - Pubmed
  • Nielsen FE, Bodvarsdottir TB, Worsaae A, MacKay P, Stidsen CE, Boonen HC, Pridal L, Arkhammar PO, Wahl P, Ynddal L, Junager F, Dragsted N, Tagmose TM, Mogensen JP, Koch A, Treppendahl SP, Hansen JB: 6-Chloro-3-alkylamino-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide derivatives potently and selectively activate ATP sensitive potassium channels of pancreatic beta-cells. J Med Chem. 2002 Sep 12;45(19):4171-87. - Pubmed
  • Babenko AP, Bryan J: SUR-dependent modulation of KATP channels by an N-terminal KIR6.2 peptide. Defining intersubunit gating interactions. J Biol Chem. 2002 Nov 15;277(46):43997-4004. Epub 2002 Sep 3. - Pubmed
  • Ueda K, Komine J, Matsuo M, Seino S, Amachi T: Cooperative binding of ATP and MgADP in the sulfonylurea receptor is modulated by glibenclamide. Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1268-72. - Pubmed
DTHybrid score 0.4225

Predictions


Id Partner name Gene Name Score
4757 Cytochrome P450 2C9 CYP2C9 0.074
781 ATP-sensitive inward rectifier potassium channel 11 KCNJ11 0.07
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0661
4209 ATP-sensitive inward rectifier potassium channel 8 KCNJ8 0.0569
238 Peroxisome proliferator-activated receptor gamma PPARG 0.0528
20 Prostaglandin G/H synthase 1 PTGS1 0.05
378 Alpha-2C adrenergic receptor ADRA2C 0.0362
1974 Oligopeptide transporter, kidney isoform SLC15A2 0.0348
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0335
6016 Cytochrome P450 2C19 CYP2C19 0.0325
587 Serum albumin ALB 0.0298
1729 Solute carrier family 22 member 6 SLC22A6 0.0285
4512 Cytochrome P450 3A4 CYP3A4 0.0246
629 Alpha-2B adrenergic receptor ADRA2B 0.0238
183 Vascular endothelial growth factor A VEGFA 0.023
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0228
318 Alpha-2A adrenergic receptor ADRA2A 0.0213
6070 Nischarin NISCH 0.0208
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0202
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0199
4924 Cytochrome P450 2C8 CYP2C8 0.0198
6178 UDP-glucuronosyltransferase 2B7 UGT2B7 0.0188
521 ATP-binding cassette transporter sub-family C member 9 ABCC9 0.0182
3961 G protein-activated inward rectifier potassium channel 4 KCNJ5 0.0171
3970 Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B 0.0169
6106 Cytochrome P450 2C18 CYP2C18 0.0161
132 ATP-binding cassette sub-family A member 1 ABCA1 0.0159
401 Glutamate [NMDA] receptor subunit zeta-1 GRIN1 0.0159
1588 Multidrug resistance protein 1 ABCB1 0.0121
6147 Solute carrier family 22 member 3 SLC22A3 0.012
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0113
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.011
6144 Solute carrier family 22 member 2 SLC22A2 0.0104
6145 Solute carrier family 22 member 1 SLC22A1 0.01
776 Bile salt export pump ABCB11 0.0092
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.008
1709 Canalicular multispecific organic anion transporter 2 ABCC3 0.0075
6143 Solute carrier family 22 member 7 SLC22A7 0.007
862 Multidrug resistance-associated protein 1 ABCC1 0.0065
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.006
738 Monocarboxylate transporter 1 SLC16A1 0.0049
340 Apoptotic protease-activating factor 1 APAF1 0.0049
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0048
2164 Multidrug resistance-associated protein 4 ABCC4 0.0044
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0044
825 Arsenical pump-driving ATPase ASNA1 0.0043
3435 Arsenical pump-driving ATPase arsA 0.0043
2105 ATP-binding cassette sub-family G member 1 ABCG1 0.0043
510 Serine/threonine-protein kinase receptor R3 ACVRL1 0.0043
733 Activin receptor type 1B ACVR1B 0.0043
745 Anti-Muellerian hormone type-2 receptor AMHR2 0.0043
486 Serine/threonine-protein kinase ALS2CR7 CDK15 0.0043
483 A-Raf proto-oncogene serine/threonine-protein kinase ARAF 0.0043
21 Beta-adrenergic receptor kinase 2 ADRBK2 0.0043
377 Beta-adrenergic receptor kinase 1 ADRBK1 0.0043
154 AFG3-like protein 2 AFG3L2 0.0043
225 NEDD8-activating enzyme E1 regulatory subunit NAE1 0.0043
395 ALK tyrosine kinase receptor Not Available 0.0043
292 Activin receptor type-1 ACVR1 0.0038
849 Activated CDC42 kinase 1 TNK2 0.0038
704 Long-chain-fatty-acid--CoA ligase 1 ACSL1 0.0038
297 Adenylate cyclase type 1 ADCY1 0.0038
821 Acetyl-coenzyme A synthetase 2-like, mitochondrial ACSS1 0.0038
386 Acetyl-coenzyme A synthetase, cytoplasmic ACSS2 0.0038
289 Cytosolic purine 5'-nucleotidase NT5C2 0.0038
6107 Cytochrome P450 3A7 CYP3A7 0.0036
748 5'-AMP-activated protein kinase catalytic subunit alpha-1 PRKAA1 0.0035
484 Tyrosine-protein kinase ABL2 ABL2 0.0035
4118 Cytochrome P450 3A5 CYP3A5 0.0034
740 Argininosuccinate synthase ASS1 0.0032
865 Argininosuccinate synthase ASS1 0.0032
2680 Argininosuccinate synthase argG 0.0032
3194 Argininosuccinate synthase argG 0.0032
242 Asparagine synthetase [glutamine-hydrolyzing] ASNS 0.0031
476 RAC-alpha serine/threonine-protein kinase AKT1 0.0031
6021 Adenosine kinase ADK 0.003
4119 Cytochrome P450 2D6 CYP2D6 0.003
661 ADP/ATP translocase 1 SLC25A4 0.0029
17 Proto-oncogene tyrosine-protein kinase ABL1 ABL1 0.0025
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