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Identification
NameMitiglinide
Accession NumberDB01252
TypeSmall Molecule
GroupsApproved, Investigational
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
Synonyms
SynonymLanguageCode
KAD-1229Not AvailableNot Available
Mitiglinide calcium hydrateNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
GlufastNot Available
Brand mixturesNot Available
Categories
CAS number145375-43-5
WeightAverage: 315.4067
Monoisotopic: 315.183443671
Chemical FormulaC19H25NO3
InChI KeyWPGGHFDDFPHPOB-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)
IUPAC Name
2-benzyl-4-(octahydro-1H-isoindol-2-yl)-4-oxobutanoic acid
SMILES
OC(=O)C(CC(=O)N1CC2CCCCC2C1)CC1=CC=CC=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassPhenylpropanoids and Polyketides
ClassPhenylpropanoic Acids
SubclassNot Available
Direct parentPhenylpropanoic Acids
Alternative parentsIsoindoles; Benzene and Substituted Derivatives; Pyrrolidines; Tertiary Carboxylic Acid Amides; Tertiary Amines; Enolates; Polyamines; Carboxylic Acids; Isoindlines
Substituentsisoindole or derivative; isoindoline; isoindole; benzene; tertiary carboxylic acid amide; pyrrolidine; tertiary amine; carboxamide group; carboxylic acid derivative; polyamine; carboxylic acid; enolate; amine; organonitrogen compound
Classification descriptionThis compound belongs to the phenylpropanoic acids. These are compounds whose structure contain a benzene ring conjugated to a propanoic acid.
Pharmacology
IndicationFor the treatment of type 2 diabetes.
PharmacodynamicsMitiglinide 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 actionMitiglinide 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9921
Blood Brain Barrier + 0.9694
Caco-2 permeable - 0.5956
P-glycoprotein substrate Substrate 0.5
P-glycoprotein inhibitor I Non-inhibitor 0.6887
P-glycoprotein inhibitor II Non-inhibitor 0.8357
Renal organic cation transporter Inhibitor 0.5235
CYP450 2C9 substrate Non-substrate 0.8241
CYP450 2D6 substrate Non-substrate 0.6396
CYP450 3A4 substrate Non-substrate 0.5135
CYP450 1A2 substrate Non-inhibitor 0.765
CYP450 2C9 substrate Non-inhibitor 0.8653
CYP450 2D6 substrate Non-inhibitor 0.9234
CYP450 2C19 substrate Non-inhibitor 0.6464
CYP450 3A4 substrate Non-inhibitor 0.8786
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8753
Ames test Non AMES toxic 0.7059
Carcinogenicity Non-carcinogens 0.95
Biodegradation Ready biodegradable 0.522
Rat acute toxicity 2.3334 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.8826
hERG inhibition (predictor II) Non-inhibitor 0.7529
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0708ALOGPS
logP3.17ALOGPS
logP2.92ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)4.62ChemAxon
pKa (Strongest Basic)-0.15ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area57.61 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity88.31 m3·mol-1ChemAxon
Polarizability35.27 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ResourceLink
KEGG DrugD01854
PubChem Compound3047758
PubChem Substance46506527
ChemSpider2310083
Therapeutic Targets DatabaseDAP000917
PharmGKBPA164748124
WikipediaMitiglinide
ATC CodesA10BX08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. ATP-binding cassette sub-family C member 8

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
ATP-binding cassette sub-family C member 8 Q09428 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: agonist

Components

Name UniProt ID Details
Peroxisome proliferator-activated receptor gamma P37231 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 1-3 P35503 Details

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

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate

Components

Name UniProt ID Details
UDP-glucuronosyltransferase 2B7 P16662 Details

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

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Drug created on March 30, 2007 12:07 / Updated on September 16, 2013 17:13