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Identification
NameVildagliptin
Accession NumberDB04876
TypeSmall Molecule
GroupsApproved, Investigational
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. Vildagliptin inhibits the inactivation of GLP-1 and GIP by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucaon release by the alpha cells of 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.

Structure
Thumb
Synonyms
SynonymLanguageCode
EQUANot AvailableNot Available
GalvusNot AvailableNot Available
JalraNot AvailableNot Available
LAF 237Not AvailableNot Available
LAF-237Not AvailableNot Available
LAF237Not AvailableNot Available
NVP-LAF-237Not AvailableNot Available
NVP-LAF237Not AvailableNot Available
VildagliptinNot AvailableNot Available
XiliarxNot AvailableNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
GalvusNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number274901-16-5
WeightAverage: 303.3993
Monoisotopic: 303.194677059
Chemical FormulaC17H25N3O2
InChI KeySYOKIDBDQMKNDQ-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[C@H]1C#N
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentAlpha amino acid amides
Alternative Parents
Substituents
  • Alpha-amino acid amide
  • N-acylpyrrolidine
  • Cyclohexylamine
  • Tertiary carboxylic acid amide
  • Tertiary alcohol
  • Pyrrolidine
  • Cyclic alcohol
  • Tertiary amine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Secondary amine
  • Nitrile
  • Carbonitrile
  • Secondary aliphatic amine
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationUsed to reduce hyperglycemia in type 2 diabetes mellitus.
PharmacodynamicsVildagliptin 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 actionVildagliptin 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.
AbsorptionRapidly absorbed following oral administration with an oral bioavailability of greater than 90%.
Volume of distributionNot Available
Protein binding9.3%
MetabolismNot Available
Route of eliminationNot Available
Half lifeThe elimination half-life is approximately 90 minutes.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrateNon-inhibitor0.6428
CYP450 2D6 substrateNon-inhibitor0.7168
CYP450 2C19 substrateNon-inhibitor0.6922
CYP450 3A4 substrateNon-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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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 Reference
  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
External Links
ATC CodesA10BH02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AripiprazoleHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Arsenic trioxideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
ArticaineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
AsenapineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
AtazanavirHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Azilsartan medoxomilThiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
BendroflumethiazideThiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
BumetanideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
BuserelinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
ChlorothiazideThiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
ChlorpropamideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
ChlorthalidoneThiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
ClozapineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
CorticotropinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Cortisone acetateHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Cyproterone acetateHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
DabrafenibHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
DanazolHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
DarunavirHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
DesogestrelHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
DiazoxideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
DisopyramideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
DrospirenoneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
EstropipateHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Ethacrynic acidHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Ethinyl EstradiolHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
EthynodiolHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
EtonogestrelHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
EverolimusHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
FludrocortisoneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
FosamprenavirHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
FurosemideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
GliclazideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
GlimepirideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
GlipizideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
GlyburideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
GoserelinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
HistrelinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
HomoharringtonineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
HydrochlorothiazideThiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
IloperidoneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
IndapamideThiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
IndinavirHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
inhaled insulinMay enhance the hypoglycemic effect of Hypoglycemic Agents.
Insulin AspartMay enhance the hypoglycemic effect of Hypoglycemic Agents.
Insulin DetemirMay enhance the hypoglycemic effect of Hypoglycemic Agents.
Insulin GlargineMay enhance the hypoglycemic effect of Hypoglycemic Agents.
Insulin GlulisineMay enhance the hypoglycemic effect of Hypoglycemic Agents.
Insulin LisproMay enhance the hypoglycemic effect of Hypoglycemic Agents.
Insulin RegularMay enhance the hypoglycemic effect of Hypoglycemic Agents.
LanreotideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
LeuprolideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
LevonorgestrelHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
LopinavirHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
LurasidoneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
MecaserminMay enhance the hypoglycemic effect of Hypoglycemic Agents.
Medroxyprogesterone AcetateHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Megestrol acetateHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
MestranolHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
MethotrimeprazineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
MethyclothiazideThiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
MethylprednisoloneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
MetolazoneThiazide Diuretics may diminish the therapeutic effect of Antidiabetic Agents.
MifepristoneMay enhance the hypoglycemic effect of Hypoglycemic Agents.
NateglinideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
NelfinavirHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
NilotinibHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
NorelgestrominHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
NorethindroneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
NorgestimateHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
OctreotideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
OlanzapineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
PaliperidoneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
PasireotideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
PentamidineMay enhance the hypoglycemic effect of Hypoglycemic Agents.
PiperazineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
PipotiazineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
PrednisoneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
ProgesteroneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
QuetiapineHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
QuinineMay enhance the hypoglycemic effect of Hypoglycemic Agents.
RepaglinideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
RisperidoneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
RitonavirHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
SaquinavirHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
SirolimusHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
SulfadiazineMay enhance the hypoglycemic effect of Hypoglycemic Agents.
SulfamethoxazoleMay enhance the hypoglycemic effect of Hypoglycemic Agents.
SulfisoxazoleMay enhance the hypoglycemic effect of Hypoglycemic Agents.
SunitinibMay enhance the hypoglycemic effect of Hypoglycemic Agents.
TemsirolimusHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
TipranavirHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
TolazamideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
TolbutamideMay enhance the hypoglycemic effect of Hypoglycemic Agents.
TorasemideHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
TriptorelinHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
VorinostatHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
ZiprasidoneHyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents.
Food InteractionsNot Available

Targets

1. Dipeptidyl peptidase 4

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
Dipeptidyl peptidase 4 P27487 Details

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
  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
  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

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Drug created on October 20, 2007 05:50 / Updated on September 16, 2013 17:26