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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
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International Brands
NameCompany
GlufastNot Available
Brand mixturesNot Available
SaltsNot 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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic acid.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassPhenylpropanoic acids
Sub ClassNot Available
Direct ParentPhenylpropanoic acids
Alternative Parents
Substituents
  • 3-phenylpropanoic-acid
  • Isoindole or derivatives
  • Isoindole
  • Isoindoline
  • N-acylpyrrolidine
  • Benzenoid
  • Monocyclic benzene moiety
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Tertiary amine
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
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
MetabolismNot Available
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
PropertyValueProbability
Human Intestinal Absorption+0.9921
Blood Brain Barrier+0.9694
Caco-2 permeable-0.5956
P-glycoprotein substrateSubstrate0.5
P-glycoprotein inhibitor INon-inhibitor0.6887
P-glycoprotein inhibitor IINon-inhibitor0.8357
Renal organic cation transporterInhibitor0.5235
CYP450 2C9 substrateNon-substrate0.8241
CYP450 2D6 substrateNon-substrate0.6396
CYP450 3A4 substrateNon-substrate0.5135
CYP450 1A2 substrateNon-inhibitor0.765
CYP450 2C9 substrateNon-inhibitor0.8653
CYP450 2D6 substrateNon-inhibitor0.9234
CYP450 2C19 substrateNon-inhibitor0.6464
CYP450 3A4 substrateNon-inhibitor0.8786
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8753
Ames testNon AMES toxic0.7059
CarcinogenicityNon-carcinogens0.95
BiodegradationReady biodegradable0.522
Rat acute toxicity2.3334 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8826
hERG inhibition (predictor II)Non-inhibitor0.7529
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0708 mg/mLALOGPS
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferenceNot Available
External Links
ATC CodesA10BX08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcarboseAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
AlbiglutideAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
AlogliptinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
BromocriptineAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
CanagliflozinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
ChlorpropamideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
DapagliflozinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
DisopyramideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
DulaglutideAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
EmpagliflozinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
ExenatideAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
GliclazideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
GlimepirideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
GlipizideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
GlyburideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
inhaled insulinMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin AspartMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin DetemirMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin GlargineMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin GlulisineMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin LisproMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
Insulin RegularMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
LanreotideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
LinagliptinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
LiraglutideAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
MecaserminMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
MetforminAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
MifepristoneMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
MiglitolAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
NateglinideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
OctreotideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
PasireotideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
PentamidineMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
PioglitazoneAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
PramlintideAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
QuinineMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
RepaglinideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
RosiglitazoneAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
SaxagliptinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
SitagliptinAntidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemic Agents.
SulfadiazineMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
SulfamethoxazoleMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
SulfisoxazoleMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
SunitinibMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
TolazamideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
TolbutamideMay enhance the hypoglycemic effect of other Hypoglycemic Agents.
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