Identification

Name
Voglibose
Accession Number
DB04878
Type
Small Molecule
Groups
Investigational
Description

Voglibose (INN and USAN) is an alpha-glucosidase inhibitor used for lowering post-prandial blood glucose levels in people with diabetes mellitus. It is made in India by Ranbaxy Labs and sold under the trade name Volix. [Wikipedia]

Structure
Thumb
Synonyms
  • Basen
External IDs
A-71100 / AO-128
International/Other Brands
Basen (Takeda Chemical Industries) / Glustat / Vocarb / Volix (Ranbaxy labs)
Categories
UNII
S77P977AG8
CAS number
83480-29-9
Weight
Average: 267.2762
Monoisotopic: 267.131802031
Chemical Formula
C10H21NO7
InChI Key
FZNCGRZWXLXZSZ-CIQUZCHMSA-N
InChI
InChI=1S/C10H21NO7/c12-2-5(3-13)11-6-1-10(18,4-14)9(17)8(16)7(6)15/h5-9,11-18H,1-4H2/t6-,7-,8+,9-,10-/m0/s1
IUPAC Name
(1S,2S,3R,4S,5S)-5-[(1,3-dihydroxypropan-2-yl)amino]-1-(hydroxymethyl)cyclohexane-1,2,3,4-tetrol
SMILES
OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O

Pharmacology

Indication

For the treatment of diabetes. It is specifically used for lowering post-prandial blood glucose levels thereby reducing the risk of macrovascular complications.

Pharmacodynamics

Voglibose, an alpha-glucosidase inhibitor, is a synthetic compound with potent and enduring therapeutic efficacies against disorders of sensory, motor and autonomic nerve systems due to diabetes mellitus. The drug was approved in Japan in 1994 for the treatment of diabetes, and it is under further investigation by Takeda for the treatment of impaired glucose tolerance. Alpha-glucosidase inhibitors are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of complex carbohydrates (such as starch). Complex carbohydrates are normally converted into simple sugars (monosaccharides) which can be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of complex carbohydrates on blood sugar.

Mechanism of action

Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrates: specifically alpha-glucosidase enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine. Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine. Inhibition of these enzyme systems reduces the rate of digestion of complex carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels: the long term effect is a small reduction in hemoglobin-A1c level. (From Drug Therapy in Nursing, 2nd ed)

TargetActionsOrganism
AMaltase-glucoamylase, intestinal
inhibitor
Human
Absorption

Slowly and poorly absorbed. The reported pharmacokinetic parameters of voglibose with metformin are Cmax corresponds to 1.38 mcg/ml while AUC is 8.17 mcg.h/ml and tmax is of 2.5 hours.[4]

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Little metabolism occurs and no metabolites have as yet been identified.

Route of elimination
Not Available
Half life

The half-life of voglibose is very similar to the one found for metformin and it is reported to be of 4.08 hours.[4]

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Voglibose is combined with 2,4-thiazolidinedione.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Voglibose can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Voglibose.
AcetazolamideThe therapeutic efficacy of Voglibose can be increased when used in combination with Acetazolamide.
AcetohexamideThe risk or severity of hypoglycemia can be increased when Acetohexamide is combined with Voglibose.
Acetyl sulfisoxazoleThe therapeutic efficacy of Voglibose can be increased when used in combination with Acetyl sulfisoxazole.
Acetylsalicylic acidAcetylsalicylic acid may increase the hypoglycemic activities of Voglibose.
AgmatineThe risk or severity of hypoglycemia can be increased when Agmatine is combined with Voglibose.
AICA ribonucleotideThe risk or severity of hypoglycemia can be increased when AICA ribonucleotide is combined with Voglibose.
AlaproclateThe risk or severity of hypoglycemia can be increased when Alaproclate is combined with Voglibose.
Food Interactions
Not Available

References

Synthesis Reference

Heinz G. Floss, Sungsook Lee, Ingo Tornus, "Valiolone, a method of preparing it, and its use to prepare acarbose and voglibose." U.S. Patent US6150568, issued October, 1995.

US6150568
General References
  1. Aso Y, Yamamoto R, Suetsugu M, Matsumoto S, Wakabayashi S, Matsutomo R, Takebayashi K, Inukai T: Comparison of the effects of pioglitazone and voglibose on circulating total and high-molecular-weight adiponectin, and on two fibrinolysis inhibitors, in patients with Type 2 diabetes. Diabet Med. 2007 Sep;24(9):962-8. Epub 2007 May 17. [PubMed:17509067]
  2. Kurebayashi S, Watada H, Tanaka Y, Kawasumi M, Kawamori R, Hirose T: Efficacy and adverse effects of nateglinide in early type 2 diabetes. Comparison with voglibose in a cross-over study. Endocr J. 2006 Apr;53(2):213-7. [PubMed:16618980]
  3. Satoh N, Shimatsu A, Yamada K, Aizawa-Abe M, Suganami T, Kuzuya H, Ogawa Y: An alpha-glucosidase inhibitor, voglibose, reduces oxidative stress markers and soluble intercellular adhesion molecule 1 in obese type 2 diabetic patients. Metabolism. 2006 Jun;55(6):786-93. [PubMed:16713439]
  4. Choi HK, Oh M, Kim EJ, Song GS, Ghim JL, Shon JH, Kim HS, Shin JG: Pharmacokinetic study of metformin to compare voglibose/metformin fixed-dose combination with coadministered voglibose and metformin. Int J Clin Pharmacol Ther. 2015 Feb;53(2):147-53. doi: 10.5414/CP202197. [PubMed:25546164]
External Links
Human Metabolome Database
HMDB0015598
KEGG Drug
D01665
PubChem Compound
444020
PubChem Substance
46504462
ChemSpider
392046
BindingDB
50263044
ChEBI
32300
ChEMBL
CHEMBL476960
Therapeutic Targets Database
DAP001104
PharmGKB
PA164752433
HET
VOG
Wikipedia
Voglibose
ATC Codes
A10BF03 — Voglibose
PDB Entries
6c9x / 6c9z

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentType 2 Diabetes Mellitus2
2, 3CompletedTreatmentType 2 Diabetes Mellitus2
3CompletedTreatmentDiabetes Mellitus, Non-Insulin-Dependent2
3CompletedTreatmentType 2 Diabetes Mellitus2
4CompletedBasic ScienceType 2 Diabetes Mellitus1
4CompletedTreatmentImpaired Glucose Tolerance (IGT)1
4CompletedTreatmentType 2 Diabetes Mellitus3
4Unknown StatusTreatmentInsulin Sensitivity/Resistance / Type 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableImpaired Glucose Tolerance (IGT)1
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus3
Not AvailableTerminatedPreventionImpaired Glucose Tolerance (IGT) / Myocardial Infarction1
Not AvailableUnknown StatusPreventionCoronary Heart Disease (CHD) / Impaired Glucose Tolerance (IGT)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility190.0 mg/mLALOGPS
logP-2.3ALOGPS
logP-4.9ChemAxon
logS-0.15ALOGPS
pKa (Strongest Acidic)12.46ChemAxon
pKa (Strongest Basic)7.66ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count8ChemAxon
Polar Surface Area153.64 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity59.55 m3·mol-1ChemAxon
Polarizability26.02 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6431
Blood Brain Barrier-0.9478
Caco-2 permeable-0.7878
P-glycoprotein substrateNon-substrate0.6439
P-glycoprotein inhibitor INon-inhibitor0.8759
P-glycoprotein inhibitor IINon-inhibitor0.918
Renal organic cation transporterNon-inhibitor0.873
CYP450 2C9 substrateNon-substrate0.812
CYP450 2D6 substrateNon-substrate0.8224
CYP450 3A4 substrateNon-substrate0.663
CYP450 1A2 substrateNon-inhibitor0.8853
CYP450 2C9 inhibitorNon-inhibitor0.9232
CYP450 2D6 inhibitorNon-inhibitor0.9324
CYP450 2C19 inhibitorNon-inhibitor0.9288
CYP450 3A4 inhibitorNon-inhibitor0.9856
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9737
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.9361
BiodegradationNot ready biodegradable0.8142
Rat acute toxicity1.1572 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9395
hERG inhibition (predictor II)Non-inhibitor0.9532
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as aminocyclitols. These are cyclitols with at least one hydroxyl group replace by an amino group.
Kingdom
Organic compounds
Super Class
Organic oxygen compounds
Class
Organooxygen compounds
Sub Class
Alcohols and polyols
Direct Parent
Aminocyclitols
Alternative Parents
Cyclohexylamines / Cyclohexanols / Tertiary alcohols / 1,2-aminoalcohols / Polyols / Dialkylamines / Primary alcohols / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Aminocyclitol / Cyclohexanol / Cyclohexylamine / Tertiary alcohol / 1,2-aminoalcohol / Secondary alcohol / Secondary amine / Secondary aliphatic amine / Polyol / Organic nitrogen compound
Molecular Framework
Aliphatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Maltose alpha-glucosidase activity
Specific Function
May serve as an alternate pathway for starch digestion when luminal alpha-amylase activity is reduced because of immaturity or malnutrition. May play a unique role in the digestion of malted dietar...
Gene Name
MGAM
Uniprot ID
O43451
Uniprot Name
Maltase-glucoamylase, intestinal
Molecular Weight
209850.8 Da
References
  1. Satoh N, Shimatsu A, Yamada K, Aizawa-Abe M, Suganami T, Kuzuya H, Ogawa Y: An alpha-glucosidase inhibitor, voglibose, reduces oxidative stress markers and soluble intercellular adhesion molecule 1 in obese type 2 diabetic patients. Metabolism. 2006 Jun;55(6):786-93. [PubMed:16713439]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  3. Matsumura M, Monden T, Miyashita Y, Kawagoe Y, Shimizu H, Nakatani Y, Domeki N, Yanagi K, Ikeda S, Kasai K: Effects of changeover from voglibose to acarbose on postprandial triglycerides in type 2 diabetes mellitus patients. Adv Ther. 2009 Jun;26(6):660-6. doi: 10.1007/s12325-009-0040-7. Epub 2009 Jun 30. [PubMed:19568704]
  4. Abe M, Okada K, Maruyama T, Maruyama N, Matsumoto K: Combination therapy with mitiglinide and voglibose improves glycemic control in type 2 diabetic patients on hemodialysis. Expert Opin Pharmacother. 2010 Feb;11(2):169-76. doi: 10.1517/14656560903530683. [PubMed:20025554]
  5. Iwasa M, Kobayashi H, Yasuda S, Kawamura I, Sumi S, Yamada Y, Shiraki T, Yamaki T, Ushikoshi H, Aoyama T, Nishigaki K, Takemura G, Fujiwara T, Fujiwara H, Minatoguchi S: Antidiabetic drug voglibose is protective against ischemia-reperfusion injury through glucagon-like peptide 1 receptors and the phosphoinositide 3-kinase-Akt-endothelial nitric oxide synthase pathway in rabbits. J Cardiovasc Pharmacol. 2010 Jun;55(6):625-34. doi: 10.1097/FJC.0b013e3181dcd240. [PubMed:20351564]
  6. Fujimori Y, Katsuno K, Ojima K, Nakashima I, Nakano S, Ishikawa-Takemura Y, Kusama H, Isaji M: Sergliflozin etabonate, a selective SGLT2 inhibitor, improves glycemic control in streptozotocin-induced diabetic rats and Zucker fatty rats. Eur J Pharmacol. 2009 May 1;609(1-3):148-54. doi: 10.1016/j.ejphar.2009.03.007. Epub 2009 Mar 10. [PubMed:19281809]

Drug created on October 20, 2007 12:23 / Updated on November 02, 2018 06:06