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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
SynonymsNot Available
External Identifiers
  • KAD-1229
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
GlufastNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Mitiglinide calcium dihydrate
207844-01-7
Thumb
  • InChI Key: QEVLNUAVAONTEW-UZYHXJQGSA-L
  • Monoisotopic Mass: 704.3349575
  • Average Mass: 704.918
DBSALT001868
Categories
UNIID86I0XLB13
CAS number145375-43-5
WeightAverage: 315.413
Monoisotopic: 315.183443669
Chemical FormulaC19H25NO3
InChI KeyWPGGHFDDFPHPOB-BBWFWOEESA-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)/t15-,16+,17-/m0/s1
IUPAC Name
SMILES
[H][C@@](CC(=O)N1C[C@@]2([H])CCCC[C@@]2([H])C1)(CC1=CC=CC=C1)C(O)=O
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
  • Isoindoline
  • Isoindole
  • Isoindole or derivatives
  • N-acylpyrrolidine
  • Monocyclic benzene moiety
  • Benzenoid
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Carboxamide group
  • Carboxylic acid derivative
  • Carboxylic acid
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organic nitrogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Organonitrogen compound
  • Organooxygen compound
  • 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.
Related Articles
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 inhibitorNon-inhibitor0.8653
CYP450 2D6 inhibitorNon-inhibitor0.9234
CYP450 2C19 inhibitorNon-inhibitor0.6464
CYP450 3A4 inhibitorNon-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
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 Properties
PropertyValueSource
logP2.9Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0708 mg/mLALOGPS
logP3.17ALOGPS
logS-3.6ALOGPS
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesA10BX08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Sulfonylurea receptor activity
Specific Function:
Subunit of the beta-cell ATP-sensitive potassium channel (KATP). Regulator of ATP-sensitive K(+) channels and insulin release.
Gene Name:
ABCC8
Uniprot ID:
Q09428
Molecular Weight:
176990.36 Da
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:11716850 ]
  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:17003348 ]
  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:17592198 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation...
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
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:17082235 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Retinoic acid binding
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative regulator of isoform 1.
Gene Name:
UGT1A3
Uniprot ID:
P35503
Molecular Weight:
60337.835 Da
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:19515014 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Glucuronosyltransferase activity
Specific Function:
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.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. Is also active with androsterone, hyodeoxycholic acid and tetrachlorocatechol...
Gene Name:
UGT2B7
Uniprot ID:
P16662
Molecular Weight:
60694.12 Da
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:19515014 ]
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Drug created on March 30, 2007 12:07 / Updated on May 11, 2016 08:52