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Identification
NameMitiglinide
Accession NumberDB01252
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionMitiglinide 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
(2S)-4-[(3aR,7aS)-octahydro-1H-isoindol-2-yl]-2-benzyl-4-oxobutanoic acid
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
logP2.92ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)4.62ChemAxon
pKa (Strongest Basic)-0.83ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area57.61 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity88.31 m3·mol-1ChemAxon
Polarizability34.98 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 ReferencesNot Available
External Links
ATC CodesA10BX08
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AripiprazoleThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Aripiprazole.
Arsenic trioxideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Arsenic trioxide.
ArticaineThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Articaine.
AsenapineThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Asenapine.
AtazanavirThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Atazanavir.
BendroflumethiazideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Bendroflumethiazide.
BetamethasoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Betamethasone.
BrexpiprazoleThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Brexpiprazole.
BumetanideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Bumetanide.
BuserelinThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Buserelin.
CeritinibThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Ceritinib.
ChlorothiazideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Chlorothiazide.
ChlorpropamideMitiglinide may increase the hypoglycemic activities of Chlorpropamide.
ChlorthalidoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Chlorthalidone.
ClozapineThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Clozapine.
CorticotropinThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Corticotropin.
Cortisone acetateThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Cortisone acetate.
Cyproterone acetateThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Cyproterone acetate.
DabrafenibThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Dabrafenib.
DanazolThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Danazol.
DarunavirThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Darunavir.
DesogestrelThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Desogestrel.
DexamethasoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Dexamethasone.
DiazoxideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Diazoxide.
DienogestThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Dienogest.
DisopyramideMitiglinide may increase the hypoglycemic activities of Disopyramide.
DrospirenoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Drospirenone.
EpinephrineThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Epinephrine.
EstradiolThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Estradiol.
Estrone sulfateThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Estrone sulfate.
Etacrynic acidThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Etacrynic acid.
Ethinyl EstradiolThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Ethinyl Estradiol.
Ethynodiol diacetateThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Ethynodiol diacetate.
EtonogestrelThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Etonogestrel.
EverolimusThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Everolimus.
FludrocortisoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Fludrocortisone.
FosamprenavirThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Fosamprenavir.
FurosemideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Furosemide.
GliclazideMitiglinide may increase the hypoglycemic activities of Gliclazide.
GlimepirideMitiglinide may increase the hypoglycemic activities of Glimepiride.
GlipizideMitiglinide may increase the hypoglycemic activities of Glipizide.
GlyburideMitiglinide may increase the hypoglycemic activities of Glyburide.
GoserelinThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Goserelin.
HistrelinThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Histrelin.
HydrochlorothiazideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Hydrochlorothiazide.
HydrocortisoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Hydrocortisone.
HydroflumethiazideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Hydroflumethiazide.
Hydroxyprogesterone caproateThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Hydroxyprogesterone caproate.
IloperidoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Iloperidone.
IndapamideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Indapamide.
IndinavirThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Indinavir.
Insulin AspartMitiglinide may increase the hypoglycemic activities of Insulin Aspart.
Insulin DetemirMitiglinide may increase the hypoglycemic activities of Insulin Detemir.
Insulin GlargineMitiglinide may increase the hypoglycemic activities of Insulin Glargine.
Insulin GlulisineMitiglinide may increase the hypoglycemic activities of Insulin Glulisine.
Insulin HumanMitiglinide may increase the hypoglycemic activities of Insulin Human.
Insulin LisproMitiglinide may increase the hypoglycemic activities of Insulin Lispro.
LanreotideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Lanreotide.
LanreotideMitiglinide may increase the hypoglycemic activities of Lanreotide.
LeuprolideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Leuprolide.
LevonorgestrelThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Levonorgestrel.
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Mitiglinide.
LopinavirThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Lopinavir.
LurasidoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Lurasidone.
MecaserminMitiglinide may increase the hypoglycemic activities of Mecasermin.
Medroxyprogesterone acetateThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Medroxyprogesterone acetate.
Megestrol acetateThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Megestrol acetate.
MestranolThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Mestranol.
MethotrimeprazineThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Methotrimeprazine.
MethyclothiazideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Methyclothiazide.
MethylprednisoloneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Methylprednisolone.
MetolazoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Metolazone.
MifepristoneMitiglinide may increase the hypoglycemic activities of Mifepristone.
NateglinideMitiglinide may increase the hypoglycemic activities of Nateglinide.
NelfinavirThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Nelfinavir.
NiacinThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Niacin.
NilotinibThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Nilotinib.
NorethisteroneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Norethisterone.
NorgestimateThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Norgestimate.
OctreotideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Octreotide.
OctreotideMitiglinide may increase the hypoglycemic activities of Octreotide.
OlanzapineThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Olanzapine.
PaliperidoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Paliperidone.
PasireotideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Pasireotide.
PasireotideMitiglinide may increase the hypoglycemic activities of Pasireotide.
PentamidineThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Pentamidine.
PentamidineMitiglinide may increase the hypoglycemic activities of Pentamidine.
PiperazineThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Piperazine.
PipotiazineThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Pipotiazine.
PolythiazideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Polythiazide.
PrednisoloneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Prednisolone.
PrednisoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Prednisone.
ProgesteroneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Progesterone.
QuetiapineThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Quetiapine.
QuinethazoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Quinethazone.
QuinineMitiglinide may increase the hypoglycemic activities of Quinine.
RepaglinideMitiglinide may increase the hypoglycemic activities of Repaglinide.
RisperidoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Risperidone.
RitonavirThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Ritonavir.
SaquinavirThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Saquinavir.
SirolimusThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Sirolimus.
SulfadiazineMitiglinide may increase the hypoglycemic activities of Sulfadiazine.
SulfamethoxazoleMitiglinide may increase the hypoglycemic activities of Sulfamethoxazole.
SulfisoxazoleMitiglinide may increase the hypoglycemic activities of Sulfisoxazole.
SunitinibMitiglinide may increase the hypoglycemic activities of Sunitinib.
TacrolimusThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Tacrolimus.
TemsirolimusThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Temsirolimus.
TipranavirThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Tipranavir.
TolazamideMitiglinide may increase the hypoglycemic activities of Tolazamide.
TolbutamideMitiglinide may increase the hypoglycemic activities of Tolbutamide.
TorasemideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Torasemide.
TriamcinoloneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Triamcinolone.
TrichlormethiazideThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Trichlormethiazide.
TriptorelinThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Triptorelin.
VorinostatThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Vorinostat.
ZiprasidoneThe therapeutic efficacy of Mitiglinide can be decreased when used in combination with Ziprasidone.
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 August 17, 2016 12:23