Vildagliptin

Identification

Name
Vildagliptin
Accession Number
DB04876
Description

Vildagliptin, previously identified as LAF237, is a new oral anti-hyperglycemic agent (anti-diabetic drug) of the new dipeptidyl peptidase-4 (DPP-4) inhibitor class of drugs. Vidagliptin subsequently acts by inhibiting the inactivation of glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) by DPP-4. This inhibitory activity ultimately results in a two-fold action where GLP-1 and GIP are present to potentiate the secretion of insulin by beta cells and suppress glucagon secretion by alpha cells in the islets of Langerhans in the pancreas. It is currently in clinical trials in the U.S. and has been shown to reduce hyperglycemia in type 2 diabetes mellitus. While the drug is still not approved for use in the US, it was approved in Feb 2008 by European Medicines Agency for use within the EU and is listed on the Australian PBS with certain restrictions.

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 303.3993
Monoisotopic: 303.194677059
Chemical Formula
C17H25N3O2
Synonyms
  • Vildagliptin
  • Vildagliptina
External IDs
  • LAF 237
  • LAF-237
  • LAF237
  • NVP-LAF 237
  • NVP-LAF-237
  • NVP-LAF237

Pharmacology

Indication

Used to reduce hyperglycemia in type 2 diabetes mellitus.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Vildagliptin belongs to a class of orally active antidiabetic drugs (DPP-IV inhibitors) that appear to have multiple functional benefits beyond simple blood-glucose control. One of these is a potential protective effect on pancreatic beta cells, which deteriorate in diabetes. Vildagliptin appears to be safe, very well tolerated, and efficacious. Following a meal, gut incretin hormones are released. The most important incretin hormones are GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). These hormones, secreted in the human small intestine, are responsible for insulin release due to increased glucose levels. In contrast to agents that promote insulin secretion via glucose-independent mechanisms, GLP-1's dependence on glucose concentration is considered beneficial due to a lower risk of hypoglycemia. GLP-1 also inhibits glucagon secretion and increases beta cell mass by stimulating proliferation and neogenesis. However, the clinical utility of GLP-1 is limited by its short half-life (2 minutes). GLP-1 is rapidly degraded by the proteolytic enzyme DPP-IV. To enhance GLP-1 activity, inhibition of the DPP-IV enzyme is emerging as a novel therapeutic approach in the treatment of diabetes. Administration of vildagliptin enhances GLP-1's ability to produce insulin in response to elevated concentrations of blood glucose, inhibit the release of glucagon following meals, slow the rate of nutrient absorption into the bloodstream, slow the rate of gastric emptying, and reduce food intake.

Mechanism of action

Vildagliptin inhibits dipeptidyl peptidase-4 (DPP-4). This in turn inhibits the inactivation of GLP-1 by DPP-4, allowing GLP-1 to potentiate the secretion of insulin in the beta cells. Dipeptidyl peptidase-4's role in blood glucose regulation is thought to be through degradation of GIP and the degradation of GLP-1.

TargetActionsOrganism
ADipeptidyl peptidase 4
inhibitor
Humans
Absorption

Rapidly absorbed following oral administration with an oral bioavailability of greater than 90%.

Volume of distribution
Not Available
Protein binding

9.3%

Metabolism
Not Available
Route of elimination
Not Available
Half-life

The elimination half-life is approximately 90 minutes.

Clearance
Not Available
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity
Not Available
Affected organisms
  • Humans and other mammals
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
AcarboseThe risk or severity of hypoglycemia can be increased when Acarbose is combined with Vildagliptin.
AcebutololThe therapeutic efficacy of Vildagliptin can be increased when used in combination with Acebutolol.
AcetazolamideThe therapeutic efficacy of Vildagliptin can be increased when used in combination with Acetazolamide.
AcetohexamideVildagliptin may increase the hypoglycemic activities of Acetohexamide.
Acetyl sulfisoxazoleThe therapeutic efficacy of Vildagliptin can be increased when used in combination with Acetyl sulfisoxazole.
Acetylsalicylic acidThe risk or severity of hypoglycemia can be increased when Acetylsalicylic acid is combined with Vildagliptin.
AlbiglutideThe risk or severity of hypoglycemia can be increased when Vildagliptin is combined with Albiglutide.
AlclometasoneThe risk or severity of hyperglycemia can be increased when Alclometasone is combined with Vildagliptin.
AlogliptinThe risk or severity of angioedema can be increased when Vildagliptin is combined with Alogliptin.
AlteplaseThe risk or severity of angioedema can be increased when Alteplase is combined with Vildagliptin.
Additional Data Available
  • Extended Description
    Extended Description
    Available for Purchase

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
    Available for Purchase

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
    Available for Purchase

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

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  • Action
    Action
    Available for Purchase

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with or without food.

Products

Purchasing individual compounds or compound libraries for your research?
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International/Other Brands
EQUA
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
GalvusTablet50 mgOralNovartis Europharm Limited2007-09-26Not applicableEU flag
GalvusTablet50 mgOralNovartis Europharm Limited2007-09-26Not applicableEU flag
GalvusTablet50 mgOralNovartis Europharm Limited2007-09-26Not applicableEU flag
GalvusTablet50 mgOralNovartis Europharm Limited2007-09-26Not applicableEU flag
GalvusTablet50 mgOralNovartis Europharm Limited2007-09-26Not applicableEU flag
GalvusTablet50 mgOralNovartis Europharm Limited2007-09-26Not applicableEU flag
GalvusTablet50 mgOralNovartis Europharm Limited2007-09-26Not applicableEU flag
GalvusTablet50 mgOralNovartis Europharm Limited2007-09-26Not applicableEU flag
GalvusTablet50 mgOralNovartis Europharm Limited2007-09-26Not applicableEU flag
GalvusTablet50 mgOralNovartis Europharm Limited2007-09-26Not applicableEU flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
A10BH02 — VildagliptinA10BD08 — Metformin and vildagliptin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Alpha amino acid amides
Alternative Parents
N-acylpyrrolidines / Tertiary carboxylic acid amides / Tertiary alcohols / Cyclic alcohols and derivatives / Nitriles / Dialkylamines / Azacyclic compounds / Organopnictogen compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
Alcohol / Aliphatic heteropolycyclic compound / Alpha-amino acid amide / Amine / Azacycle / Carbonitrile / Carbonyl group / Carboxamide group / Cyclic alcohol / Hydrocarbon derivative
show 14 more
Molecular Framework
Aliphatic heteropolycyclic compounds
External Descriptors
Not Available

Chemical Identifiers

UNII
I6B4B2U96P
CAS number
274901-16-5
InChI Key
SYOKIDBDQMKNDQ-XWTIBIIYSA-N
InChI
InChI=1S/C17H25N3O2/c18-9-14-2-1-3-20(14)15(21)10-19-16-5-12-4-13(6-16)8-17(22,7-12)11-16/h12-14,19,22H,1-8,10-11H2/t12?,13?,14-,16?,17?/m0/s1
IUPAC Name
(2S)-1-{2-[(3-hydroxyadamantan-1-yl)amino]acetyl}pyrrolidine-2-carbonitrile
SMILES
OC12CC3CC(C1)CC(C3)(C2)NCC(=O)N1CCC[[email protected]]1C#N

References

Synthesis Reference

Stephen Winter, Jordi Bosch, Jordi Puig Serrano, Jose Javier Soto, "PROCESS FOR PREPARING VILDAGLIPTIN." U.S. Patent US20080167479, issued July 10, 2008.

US20080167479
General References
  1. Balas B, Baig MR, Watson C, Dunning BE, Ligueros-Saylan M, Wang Y, He YL, Darland C, Holst JJ, Deacon CF, Cusi K, Mari A, Foley JE, DeFronzo RA: The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. J Clin Endocrinol Metab. 2007 Apr;92(4):1249-55. Epub 2007 Jan 23. [PubMed:17244786]
Human Metabolome Database
HMDB0015596
PubChem Compound
6918537
PubChem Substance
99443227
ChemSpider
5293734
BindingDB
11695
RxNav
596554
ChEBI
135285
ChEMBL
CHEMBL142703
PharmGKB
PA165958346
Wikipedia
Vildagliptin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedBasic ScienceDiabetes1
4CompletedBasic ScienceDiabetes / Hypoglycemia1
4CompletedBasic ScienceType 2 Diabetes Mellitus3
4CompletedTreatment1- Microvascular Function / 2-oxidative Stress / 3-inflammation1
4CompletedTreatmentChronic Foot Ulcers1
4CompletedTreatmentCongestive Heart Failure (CHF) / Type 2 Diabetes Mellitus1
4CompletedTreatmentCoronary Artery Disease (CAD) / Type 2 Diabetes Mellitus1
4CompletedTreatmentDiabetes1
4CompletedTreatmentDiabetes Mellitus, Non-Insulin-Dependent / Type 2 Diabetes Mellitus1
4CompletedTreatmentElderly / Type 2 Diabetes Mellitus1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Tablet, coatedOral1000 mg
TabletOral50 mg
Tablet, coatedOral1 g
Tablet, coatedOral500 mg
Tablet, film coatedOral
Capsule50 mg
Tablet, coatedOral850 mg
Tablet, coatedOral50 mg
Tablet, film coatedOral50 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.75 mg/mLALOGPS
logP1.12ALOGPS
logP-0.22ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)14.71ChemAxon
pKa (Strongest Basic)9.03ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area76.36 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity82 m3·mol-1ChemAxon
Polarizability33.17 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9313
Blood Brain Barrier+0.7886
Caco-2 permeable-0.6768
P-glycoprotein substrateSubstrate0.6301
P-glycoprotein inhibitor IInhibitor0.5624
P-glycoprotein inhibitor IIInhibitor0.9723
Renal organic cation transporterNon-inhibitor0.6373
CYP450 2C9 substrateNon-substrate0.7472
CYP450 2D6 substrateNon-substrate0.6984
CYP450 3A4 substrateSubstrate0.5965
CYP450 1A2 substrateNon-inhibitor0.8627
CYP450 2C9 inhibitorNon-inhibitor0.6428
CYP450 2D6 inhibitorNon-inhibitor0.7168
CYP450 2C19 inhibitorNon-inhibitor0.6922
CYP450 3A4 inhibitorNon-inhibitor0.866
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5
Ames testNon AMES toxic0.7053
CarcinogenicityNon-carcinogens0.8895
BiodegradationNot ready biodegradable0.9959
Rat acute toxicity2.4274 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.853
hERG inhibition (predictor II)Inhibitor0.6939
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
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0109000000-f6f13525e0841cb9a0ce
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0902000000-39449b9fce86086b9f42
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0900000000-e42a57f8c41f08f0fe2b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0udi-0900000000-bdf96b3bb5758ccb2ee2
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0ue9-0900000000-813cd0c1f6616a3aac1a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0309000000-4cc7261ec4a8a5eb3c50
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-0901000000-2828160e08a306467998
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0udi-5900000000-797e5126c08d2be98d02
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0f6t-9600000000-55a58d88d2018c5adff8
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-9200000000-b511fd9b2243cdaf69cc
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0005-9100000000-5c5cb1119f70d6852572
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0udi-1709000000-d62dc38a0bb019fd4bed

Targets

Details
1. Dipeptidyl peptidase 4
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Virus receptor activity
Specific Function
Cell surface glycoprotein receptor involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Acts as a positive regulator of T-cell coactivation, by bindi...
Gene Name
DPP4
Uniprot ID
P27487
Uniprot Name
Dipeptidyl peptidase 4
Molecular Weight
88277.935 Da
References
  1. Ahren B, Gomis R, Standl E, Mills D, Schweizer A: Twelve- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 in metformin-treated patients with type 2 diabetes. Diabetes Care. 2004 Dec;27(12):2874-80. [PubMed:15562200]
  2. Mentlein R, Gallwitz B, Schmidt WE: Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1(7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem. 1993 Jun 15;214(3):829-35. [PubMed:8100523]
  3. Gupta R, Walunj SS, Tokala RK, Parsa KV, Singh SK, Pal M: Emerging drug candidates of dipeptidyl peptidase IV (DPP IV) inhibitor class for the treatment of Type 2 Diabetes. Curr Drug Targets. 2009 Jan;10(1):71-87. [PubMed:19149538]

Drug created on October 20, 2007 05:50 / Updated on June 12, 2020 10:52

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