Banner
targets (1)
for drugs
Identification
Name Vildagliptin
Accession Number DB04876
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
EQUA
Galvus
Jalra
LAF 237
LAF237
NVP-LAF-237
NVP-LAF237
Xiliarx
Salts Not Available
Brand names
Name Company
Galvus
Brand mixtures Not Available
Categories
  • Hypoglycemic Agents
  • Antidiabetic
CAS number 274901-16-5
Weight Average: 303.3993
Monoisotopic: 303.194677059
Chemical Formula C17H25N3O2
InChI Key InChIKey=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
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Adamantanes
Substructures
  • Hydroxy Compounds
  • Aliphatic and Aryl Amines
  • Amino Ketones
  • Nitriles and Derivatives
  • Pyrrolidines
  • Adamantanes
  • Cyanides
  • Alcohols and Polyols
  • Heterocyclic compounds
  • Carboxamides and Derivatives
  • Cyclooctane and Derivatives
Pharmacology
Indication Used to reduce hyperglycemia in type 2 diabetes mellitus.
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.
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
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
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
Property Value Source
water solubility 1.75e+00 g/l ALOGPS
logP 1.12 ALOGPS
logP -0.22 ChemAxon
logS -2.2 ALOGPS
pKa (strongest acidic) 14.71 ChemAxon
pKa (strongest basic) 9.03 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 76.36 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 82 ChemAxon
polarizability 33.17 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
PubChem Compound 6918537 Link_out
PubChem Substance 99443227 Link_out
ChemSpider 5293734 Link_out
BindingDB 11695 Link_out
PharmGKB PA165958346 Link_out
Wikipedia http://en.wikipedia.org/wiki/Vildagliptin Link_out
ATC Codes
  • A10BH02
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Dipeptidyl peptidase 4

Pharmacological action: yes
Actions: inhibitor

Removes N-terminal dipeptides sequentially from polypeptides having unsubstituted N-termini provided that the penultimate residue is proline. Plays a role in T-cell activation

Organism class: human
UniProt ID: P27487 Link_out
Gene: DPP4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on October 20, 2007 05:50 / Updated on February 08, 2013 16:23