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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
EQUA
Galvus
Jalra
LAF 237
LAF-237
LAF237
NVP-LAF-237
NVP-LAF237
Vildagliptin
Xiliarx
External Identifiers Not Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
GalvusNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIII6B4B2U96P
CAS number274901-16-5
WeightAverage: 303.3993
Monoisotopic: 303.194677059
Chemical FormulaC17H25N3O2
InChI KeyInChIKey=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
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.
Related Articles
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 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 )
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 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 ]
External Links
ATC CodesA10BD08A10BH02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AripiprazoleThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Aripiprazole.
Arsenic trioxideThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Arsenic trioxide.
ArticaineThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Articaine.
AsenapineThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Asenapine.
AtazanavirThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Atazanavir.
BendroflumethiazideThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Bendroflumethiazide.
BetamethasoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Betamethasone.
BrexpiprazoleThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Brexpiprazole.
BumetanideThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Bumetanide.
BuserelinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Buserelin.
CeritinibThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Ceritinib.
ChlorothiazideThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Chlorothiazide.
ChlorpropamideVildagliptin may increase the hypoglycemic activities of Chlorpropamide.
ChlorthalidoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Chlorthalidone.
ClozapineThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Clozapine.
CorticotropinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Corticotropin.
Cortisone acetateThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Cortisone acetate.
Cyproterone acetateThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Cyproterone acetate.
DabrafenibThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Dabrafenib.
DanazolThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Danazol.
DarunavirThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Darunavir.
DesogestrelThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Desogestrel.
DexamethasoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Dexamethasone.
DiazoxideThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Diazoxide.
DienogestThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Dienogest.
DisopyramideVildagliptin may increase the hypoglycemic activities of Disopyramide.
DrospirenoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Drospirenone.
EpinephrineThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Epinephrine.
ErythromycinVildagliptin may increase the hypoglycemic activities of Erythromycin.
EstradiolThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Estradiol.
EstropipateThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Estropipate.
Etacrynic acidThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Ethacrynic acid.
Ethinyl EstradiolThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Ethinyl Estradiol.
EthynodiolThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Ethynodiol.
EtonogestrelThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Etonogestrel.
EverolimusThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Everolimus.
FludrocortisoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Fludrocortisone.
FosamprenavirThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Fosamprenavir.
FurosemideThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Furosemide.
GliclazideVildagliptin may increase the hypoglycemic activities of Gliclazide.
GlimepirideVildagliptin may increase the hypoglycemic activities of Glimepiride.
GlipizideVildagliptin may increase the hypoglycemic activities of Glipizide.
GlyburideVildagliptin may increase the hypoglycemic activities of Glyburide.
GoserelinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Goserelin.
HistrelinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Histrelin.
HydrochlorothiazideThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Hydrochlorothiazide.
HydrocortisoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Hydrocortisone.
Hydroxyprogesterone caproateThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Hydroxyprogesterone caproate.
IloperidoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Iloperidone.
IndapamideThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Indapamide.
IndinavirThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Indinavir.
Insulin AspartVildagliptin may increase the hypoglycemic activities of Insulin Aspart.
Insulin DegludecVildagliptin may increase the hypoglycemic activities of Insulin degludec.
Insulin DetemirVildagliptin may increase the hypoglycemic activities of Insulin Detemir.
Insulin GlargineVildagliptin may increase the hypoglycemic activities of Insulin Glargine.
Insulin GlulisineVildagliptin may increase the hypoglycemic activities of Insulin Glulisine.
Insulin HumanVildagliptin may increase the hypoglycemic activities of Insulin Regular.
Insulin LisproVildagliptin may increase the hypoglycemic activities of Insulin Lispro.
LanreotideVildagliptin may increase the hypoglycemic activities of Lanreotide.
LeuprolideThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Leuprolide.
LevonorgestrelThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Levonorgestrel.
LopinavirThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Lopinavir.
LurasidoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Lurasidone.
MecaserminVildagliptin may increase the hypoglycemic activities of Mecasermin.
Medroxyprogesterone AcetateThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Medroxyprogesterone Acetate.
Megestrol acetateThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Megestrol acetate.
MestranolThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Mestranol.
MethotrimeprazineThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Methotrimeprazine.
MethyclothiazideThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Methyclothiazide.
MethylprednisoloneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Methylprednisolone.
MetolazoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Metolazone.
MifepristoneVildagliptin may increase the hypoglycemic activities of Mifepristone.
NadololThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Nadolol.
NateglinideVildagliptin may increase the hypoglycemic activities of Nateglinide.
NelfinavirThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Nelfinavir.
NiacinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Niacin.
NilotinibThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Nilotinib.
NorethisteroneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Norethindrone.
NorgestimateThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Norgestimate.
OctreotideVildagliptin may increase the hypoglycemic activities of Octreotide.
OlanzapineThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Olanzapine.
PaliperidoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Paliperidone.
PasireotideVildagliptin may increase the hypoglycemic activities of Pasireotide.
PentamidineVildagliptin may increase the hypoglycemic activities of Pentamidine.
PipotiazineThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Pipotiazine.
PrednisoloneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Prednisolone.
PrednisoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Prednisone.
ProgesteroneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Progesterone.
QuetiapineThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Quetiapine.
QuinineVildagliptin may increase the hypoglycemic activities of Quinine.
RepaglinideVildagliptin may increase the hypoglycemic activities of Repaglinide.
Repository corticotropinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Repository corticotropin.
RisperidoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Risperidone.
RitonavirThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Ritonavir.
SaquinavirThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Saquinavir.
SirolimusThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Sirolimus.
SulfadiazineVildagliptin may increase the hypoglycemic activities of Sulfadiazine.
SulfamethoxazoleVildagliptin may increase the hypoglycemic activities of Sulfamethoxazole.
SulfisoxazoleVildagliptin may increase the hypoglycemic activities of Sulfisoxazole.
SunitinibVildagliptin may increase the hypoglycemic activities of Sunitinib.
TacrolimusThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Tacrolimus.
TemsirolimusThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Temsirolimus.
TipranavirThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Tipranavir.
TolazamideVildagliptin may increase the hypoglycemic activities of Tolazamide.
TolbutamideVildagliptin may increase the hypoglycemic activities of Tolbutamide.
TorasemideThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Torasemide.
TriamcinoloneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Triamcinolone.
TrimethoprimVildagliptin may increase the hypoglycemic activities of Trimethoprim.
TriptorelinThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Triptorelin.
VorinostatThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Vorinostat.
ZiprasidoneThe therapeutic efficacy of Vildagliptin can be decreased when used in combination with Ziprasidone.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
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 binding at least ADA, CAV1, IGF2R, and PTPRC. Its binding to CAV1 and CARD11 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner. Its interaction with ADA also ...
Gene Name:
DPP4
Uniprot ID:
P27487
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 ]
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Drug created on October 20, 2007 05:50 / Updated on September 16, 2013 17:26