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targets (2) enzymes (2)
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Identification
Name Mitiglinide
Accession Number DB01252
Type small molecule
Groups approved
Description

Mitiglinide is a drug for the treatment of type 2 diabetes .Mitiglinide is thought to stimulate insulin secretion by closing the ATP-sensitive K(+) (K(ATP)) channels in pancreatic beta-cells.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
KAD-1229
Mitiglinide calcium hydrate
Salts Not Available
Brand names
Name Company
Glufast
Brand mixtures Not Available
Categories
  • Hypoglycemic Agents
CAS number 145375-43-5
Weight Average: 315.4067
Monoisotopic: 315.183443671
Chemical Formula C19H25NO3
InChI Key InChIKey=WPGGHFDDFPHPOB-UHFFFAOYSA-N
InChI
InChI=1S/C19H25NO3/c21-18(20-12-15-8-4-5-9-16(15)13-20)11-17(19(22)23)10-14-6-2-1-3-7-14/h1-3,6-7,15-17H,4-5,8-13H2,(H,22,23)
Plain Text
IUPAC Name
2-benzyl-4-(octahydro-1H-isoindol-2-yl)-4-oxobutanoic acid
SMILES
OC(=O)C(CC(=O)N1CC2CCCCC2C1)CC1=CC=CC=C1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Keto-Acids
Substructures
  • Hydroxy Compounds
  • Acetates
  • Amino Ketones
  • Pyrrolidines
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Carboxylic Acids and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Keto-Acids
Pharmacology
Indication For the treatment of type 2 diabetes.
Pharmacodynamics Mitiglinide belongs to the meglitinide class of blood glucose-lowering drugs. It is approved for use in Japan but has not yet gained FDA approval.
Mechanism of action Mitiglinide is thought to stimulate insulin secretion by binding to and blocking ATP-sensitive K(+) (K(ATP)) channels (Kir6.2/SUR1 complex, KATP channels) in pancreatic beta-cells. Closure of potassium channels causes depolarization which stimulates calcium influx through voltage-gated calcium channels. High intracellular calcium subsequently triggers the exocytosis of insulin granules.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism
Not Available
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Not Available
Affected organisms Not Available
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
Property Value Source
logP 2.9 Not Available
Predicted Properties
Property Value Source
water solubility 7.08e-02 g/l ALOGPS
logP 3.17 ALOGPS
logP 2.92 ChemAxon
logS -3.6 ALOGPS
pKa (strongest acidic) 4.62 ChemAxon
pKa (strongest basic) -0.15 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 57.61 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 88.31 ChemAxon
polarizability 35.27 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D01854 Link_out
PubChem Compound 3047758 Link_out
PubChem Substance 46506527 Link_out
ChemSpider 2310083 Link_out
Therapeutic Targets Database DAP000917 Link_out
PharmGKB PA164748124 Link_out
Wikipedia http://en.wikipedia.org/wiki/Mitiglinide Link_out
ATC Codes
  • A10BX08
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. ATP-binding cassette transporter sub-family C member 8

Pharmacological action: yes
Actions: inhibitor

Putative subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K+ channels and insulin release

Organism class: human
UniProt ID: Q09428 Link_out
Gene: ABCC8 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sunaga Y, Gonoi T, Shibasaki T, Ichikawa K, Kusama H, Yano H, Seino S: The effects of mitiglinide (KAD-1229), a new anti-diabetic drug, on ATP-sensitive K+ channels and insulin secretion: comparison with the sulfonylureas and nateglinide. Eur J Pharmacol. 2001 Nov 9;431(1):119-25. Pubmed
  2. Nagamatsu S, Ohara-Imaizumi M, Nakamichi Y, Kikuta T, Nishiwaki C: Imaging docking and fusion of insulin granules induced by antidiabetes agents: sulfonylurea and glinide drugs preferentially mediate the fusion of newcomer, but not previously docked, insulin granules. Diabetes. 2006 Oct;55(10):2819-25. Pubmed
  3. Ogawa K, Ikewaki K, Taniguchi I, Takatsuka H, Mori C, Sasaki H, Okazaki F, Shimizu M, Mochizuki S: Mitiglinide, a novel oral hypoglycemic agent, preserves the cardioprotective effect of ischemic preconditioning in isolated perfused rat hearts. Int Heart J. 2007 May;48(3):337-45. Pubmed

2. Peroxisome proliferator-activated receptor gamma

Pharmacological action: unknown
Actions: agonist

Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the receptor binds to a promoter element in the gene for acyl-CoA oxidase and activates its transcription. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis

Organism class: human
UniProt ID: P37231 Link_out
Gene: PPARG Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Scarsi M, Podvinec M, Roth A, Hug H, Kersten S, Albrecht H, Schwede T, Meyer UA, Rucker C: Sulfonylureas and glinides exhibit peroxisome proliferator-activated receptor gamma activity: a combined virtual screening and biological assay approach. Mol Pharmacol. 2007 Feb;71(2):398-406. Epub 2006 Nov 2. Pubmed
Enzymes

1. UDP-glucuronosyltransferase 1-3

Actions: substrate

UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds

UniProt ID: P35503 Link_out
Gene: UGT1A3 Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed

2. UDP-glucuronosyltransferase 2B7

Actions: substrate

Its unique specificity for 3,4-catechol estrogens and estriol suggests it may play an important role in regulating the level and activity of these potent and active estrogen metabolites

UniProt ID: P16662 Link_out
Gene: UGT2B7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. Pubmed
Comments
Drug created on March 30, 2007 12:07 / Updated on February 08, 2013 16:20