Identification

Name
Troglitazone
Accession Number
DB00197  (APRD00488)
Type
Small Molecule
Groups
Investigational, Withdrawn
Description

Troglitazone was withdrawn in 2000 due to risk of hepatotoxicity. It was superseded by pioglitazone and rosiglitazone.

Structure
Thumb
Synonyms
Not Available
International/Other Brands
Noscal / Resulin / Rezulin / Romozin
Categories
UNII
I66ZZ0ZN0E
CAS number
97322-87-7
Weight
Average: 441.54
Monoisotopic: 441.160993669
Chemical Formula
C24H27NO5S
InChI Key
GXPHKUHSUJUWKP-UHFFFAOYSA-N
InChI
InChI=1S/C24H27NO5S/c1-13-14(2)21-18(15(3)20(13)26)9-10-24(4,30-21)12-29-17-7-5-16(6-8-17)11-19-22(27)25-23(28)31-19/h5-8,19,26H,9-12H2,1-4H3,(H,25,27,28)
IUPAC Name
5-({4-[(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydro-2H-1-benzopyran-2-yl)methoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione
SMILES
CC1=C(C)C2=C(CCC(C)(COC3=CC=C(CC4SC(=O)NC4=O)C=C3)O2)C(C)=C1O

Pharmacology

Indication

For the treatment of Type II diabetes mellitus. It is used alone or in combination with a sulfonylurea, metformin, or insulin as an adjunct to diet and exercise.

Structured Indications
Not Available
Pharmacodynamics

Troglitazone is an oral antihyperglycemic agent which acts primarily by decreasing insulin resistance. Troglitazone is used in the management of type II diabetes (noninsulin-dependent diabetes mellitus (NIDDM) also known as adult-onset diabetes). It improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Troglitazone is not chemically or functionally related to either the sulfonylureas, the biguanides, or the g-glucosidase inhibitors. Troglitazone may be used concomitantly with a sulfonylurea or insulin to improve glycemic control.

Mechanism of action

Troglitazone is a thiazolidinedione antidiabetic agent that lowers blood glucose by improving target cell response to insulin. It has a unique mechanism of action that is dependent on the presence of insulin for activity. Troglitazone decreases hepatic glucose output and increases insulin dependent glucose disposal in skeletal muscle. Its mechanism of action is thought to involve binding to nuclear receptors (PPAR) that regulate the transcription of a number of insulin responsive genes critical for the control of glucose and lipid metabolism. Troglitazone is a ligand to both PPARα and PPARγ, with a highter affinity for PPARγ. The drug also contains an α-tocopheroyl moiety, potentially giving it vitamin E-like activity. Troglitazone has been shown to reduce inflammation, and is associated with a decrase in nuclear factor kappa-B (NF-κB) and a concomitant increase in its inhibitor (IκB). NF-κB is an important cellular transcription regulator for the immune response. Unlike sulfonylureas, troglitazone is not an insulin secretagogue.

TargetActionsOrganism
APeroxisome proliferator-activated receptor gamma
agonist
Human
NLong-chain-fatty-acid--CoA ligase 4
inhibitor
Human
UPlasminogen activator inhibitor 1
antagonist
Human
NEquilibrative nucleoside transporter 1
inhibitor
Human
NEstrogen-related receptor gamma
inverse agonist
Human
NSteroid hormone receptor ERR1
inverse agonist
Human
UPeroxisome proliferator-activated receptor deltaNot AvailableHuman
UPeroxisome proliferator-activated receptor alphaNot AvailableHuman
UGlutathione S-transferase PNot AvailableHuman
Absorption

Absorbed rapidly. Food increases the extent of absorption by 30% to 85%.

Volume of distribution
Not Available
Protein binding

> 99% (primarily to serum albumin)

Metabolism

A sulfate conjugate metabolite (Metabolite 1) and a quinone metabolite (Metabolite 3) have been detected in the plasma of healthy males. A glucuronide conjugate (Metabolite 2) has been detected in the urine and also in negligible amounts in the plasma. In healthy volunteers and in patients with type 2 diabetes, the steady-state concentration of Metabolite 1 is six to seven times that of troglitazone and Metabolite 3. In in vivo drug interaction studies, troglitazone has been shown to induce cytochrome P450 CYP3A4 at clinically relevant doses.

Route of elimination
Not Available
Half life

16-34 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Troglitazone can be increased when it is combined with Abiraterone.Approved
AcetohexamideTroglitazone may increase the hypoglycemic activities of Acetohexamide.Investigational, Withdrawn
AmiodaroneThe metabolism of Troglitazone can be decreased when combined with Amiodarone.Approved, Investigational
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Troglitazone.Approved, Investigational
AprepitantThe serum concentration of Troglitazone can be increased when it is combined with Aprepitant.Approved, Investigational
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Troglitazone.Approved, Investigational
ArmodafinilThe metabolism of Troglitazone can be decreased when combined with Armodafinil.Approved, Investigational
Arsenic trioxideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Arsenic trioxide.Approved, Investigational
ArticaineThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Articaine.Approved
AsenapineThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Asenapine.Approved
AtazanavirThe metabolism of Troglitazone can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Troglitazone can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Troglitazone is combined with Atorvastatin.Approved
BendroflumethiazideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Bendroflumethiazide.Approved
BetamethasoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Betamethasone.Approved, Vet Approved
BoceprevirThe metabolism of Troglitazone can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Troglitazone can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Troglitazone can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Troglitazone.Approved
BrexpiprazoleThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Brexpiprazole.Approved
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Troglitazone.Approved, Investigational
BumetanideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Bumetanide.Approved
BuserelinThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Buserelin.Approved
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Troglitazone.Approved
CapecitabineThe metabolism of Troglitazone can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Troglitazone can be increased when combined with Carbamazepine.Approved, Investigational
CarbutamideTroglitazone may increase the hypoglycemic activities of Carbutamide.Experimental
CelecoxibThe metabolism of Troglitazone can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Troglitazone can be increased when it is combined with Ceritinib.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Troglitazone.Withdrawn
ChloramphenicolThe metabolism of Troglitazone can be decreased when combined with Chloramphenicol.Approved, Vet Approved
ChlorothiazideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Chlorothiazide.Approved, Vet Approved
ChlorpropamideTroglitazone may increase the hypoglycemic activities of Chlorpropamide.Approved
ChlorthalidoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Chlorthalidone.Approved
CholecalciferolThe metabolism of Troglitazone can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
Cholic AcidTroglitazone may decrease the excretion rate of Cholic Acid which could result in a higher serum level.Approved
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Troglitazone.Approved
CimetidineThe metabolism of Troglitazone can be decreased when combined with Cimetidine.Approved
CitalopramThe metabolism of Troglitazone can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Troglitazone can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Troglitazone can be decreased when combined with Clemastine.Approved
ClotrimazoleThe metabolism of Troglitazone can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Clozapine.Approved
CobicistatThe metabolism of Troglitazone can be decreased when combined with Cobicistat.Approved
ConivaptanThe serum concentration of Troglitazone can be increased when it is combined with Conivaptan.Approved, Investigational
CorticotropinThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Corticotropin.Approved, Vet Approved
Cortisone acetateThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Cortisone acetate.Approved
CrisaboroleThe metabolism of Troglitazone can be decreased when combined with Crisaborole.Approved
CrizotinibThe metabolism of Troglitazone can be decreased when combined with Crizotinib.Approved
CyclopenthiazideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Cyclopenthiazide.Experimental
CyclosporineThe metabolism of Troglitazone can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
Cyproterone acetateThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Cyproterone acetate.Approved, Investigational
DabrafenibThe serum concentration of Troglitazone can be decreased when it is combined with Dabrafenib.Approved
DanazolThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Danazol.Approved
DarunavirThe metabolism of Troglitazone can be decreased when combined with Darunavir.Approved
DasatinibThe serum concentration of Troglitazone can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Troglitazone can be decreased when it is combined with Deferasirox.Approved, Investigational
DeferiproneThe serum concentration of Deferiprone can be increased when it is combined with Troglitazone.Approved
DelavirdineThe metabolism of Troglitazone can be decreased when combined with Delavirdine.Approved
DesogestrelThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Desogestrel.Approved
DexamethasoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Dexamethasone.Approved, Investigational, Vet Approved
DiazoxideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Diazoxide.Approved
DienogestThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Dienogest.Approved
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Troglitazone.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Troglitazone.Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Troglitazone.Experimental
DihydroergotamineThe metabolism of Troglitazone can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Troglitazone can be decreased when combined with Diltiazem.Approved
DisopyramideTroglitazone may increase the hypoglycemic activities of Disopyramide.Approved
DosulepinThe metabolism of Troglitazone can be decreased when combined with Dosulepin.Approved
DoxycyclineThe metabolism of Troglitazone can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Troglitazone can be decreased when combined with Dronedarone.Approved
DrospirenoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Drospirenone.Approved
EfavirenzThe metabolism of Troglitazone can be decreased when combined with Efavirenz.Approved, Investigational
EnzalutamideThe serum concentration of Troglitazone can be decreased when it is combined with Enzalutamide.Approved
EpinephrineThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Epinephrine.Approved, Vet Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Troglitazone.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Troglitazone.Approved
ErythromycinThe metabolism of Troglitazone can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe metabolism of Troglitazone can be decreased when combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Troglitazone can be decreased when combined with Esomeprazole.Approved, Investigational
EstradiolThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Estradiol.Approved, Investigational, Vet Approved
Estrone sulfateThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Estrone sulfate.Approved
Etacrynic acidThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Etacrynic acid.Approved
Ethinyl EstradiolThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Ethinyl Estradiol.Approved
Ethynodiol diacetateThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Ethynodiol diacetate.Approved
EtonogestrelThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Etonogestrel.Approved, Investigational
EtravirineThe metabolism of Troglitazone can be decreased when combined with Etravirine.Approved
EverolimusThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Everolimus.Approved
FelodipineThe metabolism of Troglitazone can be decreased when combined with Felodipine.Approved, Investigational
FloxuridineThe metabolism of Troglitazone can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Troglitazone can be decreased when combined with Fluconazole.Approved
FludrocortisoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Fludrocortisone.Approved
FluorouracilThe metabolism of Troglitazone can be decreased when combined with Fluorouracil.Approved
FluoxetineThe metabolism of Troglitazone can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvastatinThe metabolism of Troglitazone can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Troglitazone can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Troglitazone can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Troglitazone can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Troglitazone can be increased when combined with Fosphenytoin.Approved
FurosemideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Furosemide.Approved, Vet Approved
Fusidic AcidThe serum concentration of Troglitazone can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe metabolism of Troglitazone can be decreased when combined with Gemfibrozil.Approved
GlibornurideTroglitazone may increase the hypoglycemic activities of Glibornuride.Investigational, Withdrawn
GliclazideTroglitazone may increase the hypoglycemic activities of Gliclazide.Approved
GlimepirideTroglitazone may increase the hypoglycemic activities of Glimepiride.Approved
GlipizideTroglitazone may increase the hypoglycemic activities of Glipizide.Approved
GliquidoneTroglitazone may increase the hypoglycemic activities of Gliquidone.Approved, Investigational
GlisoxepideTroglitazone may increase the hypoglycemic activities of Glisoxepide.Approved, Investigational
GlyburideTroglitazone may increase the hypoglycemic activities of Glyburide.Approved
GoserelinThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Goserelin.Approved
HistrelinThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Histrelin.Approved
HydrochlorothiazideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Hydrochlorothiazide.Approved, Vet Approved
HydrocortisoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Hydrocortisone.Approved, Vet Approved
HydroflumethiazideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Hydroflumethiazide.Approved, Investigational
Hydroxyprogesterone caproateThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Hydroxyprogesterone caproate.Approved
IloperidoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Iloperidone.Approved
ImatinibThe metabolism of Troglitazone can be decreased when combined with Imatinib.Approved
IndapamideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Indapamide.Approved
IndinavirThe metabolism of Troglitazone can be decreased when combined with Indinavir.Approved
Insulin AspartTroglitazone may increase the hypoglycemic activities of Insulin Aspart.Approved
Insulin DetemirTroglitazone may increase the hypoglycemic activities of Insulin Detemir.Approved
Insulin GlargineTroglitazone may increase the hypoglycemic activities of Insulin Glargine.Approved
Insulin GlulisineTroglitazone may increase the hypoglycemic activities of Insulin Glulisine.Approved
Insulin HumanTroglitazone may increase the hypoglycemic activities of Insulin Human.Approved, Investigational
Insulin LisproTroglitazone may increase the hypoglycemic activities of Insulin Lispro.Approved
IrbesartanThe metabolism of Troglitazone can be decreased when combined with Irbesartan.Approved, Investigational
IsavuconazoniumThe metabolism of Troglitazone can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Troglitazone can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Troglitazone can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Troglitazone can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Troglitazone can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Troglitazone can be decreased when combined with Ketoconazole.Approved, Investigational
LanreotideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Lanreotide.Approved
LapatinibThe metabolism of Troglitazone can be decreased when combined with Lapatinib.Approved, Investigational
LeflunomideThe metabolism of Troglitazone can be decreased when combined with Leflunomide.Approved, Investigational
LeuprolideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Leuprolide.Approved, Investigational
LevonorgestrelThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Levonorgestrel.Approved, Investigational
Lipoic AcidLipoic Acid may increase the hypoglycemic activities of Troglitazone.Approved, Nutraceutical
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Troglitazone.Approved, Investigational
LobeglitazoneThe metabolism of Troglitazone can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe metabolism of Troglitazone can be decreased when combined with Lopinavir.Approved
LosartanThe metabolism of Troglitazone can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Troglitazone can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Troglitazone can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Troglitazone can be increased when it is combined with Lumacaftor.Approved
LurasidoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Lurasidone.Approved
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Troglitazone.Illicit, Investigational, Withdrawn
ManidipineThe metabolism of Troglitazone can be decreased when combined with Manidipine.Approved, Investigational
MecaserminTroglitazone may increase the hypoglycemic activities of Mecasermin.Approved, Investigational
Medroxyprogesterone acetateThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Medroxyprogesterone acetate.Approved, Investigational
Megestrol acetateThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Megestrol acetate.Approved, Vet Approved
MestranolThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Mestranol.Approved
MetahexamideTroglitazone may increase the hypoglycemic activities of Metahexamide.Experimental
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Troglitazone.Experimental
MethotrimeprazineThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Methotrimeprazine.Approved
MethyclothiazideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Methyclothiazide.Approved
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Troglitazone.Approved
MethylprednisoloneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Methylprednisolone.Approved, Vet Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Troglitazone.Approved
MetolazoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Metolazone.Approved
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Troglitazone.Experimental
MidostaurinThe metabolism of Troglitazone can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Troglitazone can be increased when it is combined with Mifepristone.Approved, Investigational
MitotaneThe serum concentration of Troglitazone can be decreased when it is combined with Mitotane.Approved
MoclobemideThe metabolism of Troglitazone can be decreased when combined with Moclobemide.Approved
ModafinilThe metabolism of Troglitazone can be decreased when combined with Modafinil.Approved, Investigational
NateglinideTroglitazone may increase the hypoglycemic activities of Nateglinide.Approved, Investigational
NefazodoneThe metabolism of Troglitazone can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Troglitazone can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Troglitazone can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Troglitazone can be increased when combined with Nevirapine.Approved
NiacinThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Niacin.Approved, Investigational, Nutraceutical
NicardipineThe metabolism of Troglitazone can be decreased when combined with Nicardipine.Approved
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Troglitazone.Approved, Investigational
NilotinibThe metabolism of Troglitazone can be decreased when combined with Nilotinib.Approved, Investigational
NorethisteroneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Norethisterone.Approved
NorgestimateThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Norgestimate.Approved
OctreotideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Octreotide.Approved, Investigational
OlanzapineThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Olanzapine.Approved, Investigational
OlaparibThe metabolism of Troglitazone can be decreased when combined with Olaparib.Approved
OmeprazoleThe metabolism of Troglitazone can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Troglitazone can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Troglitazone can be increased when it is combined with Palbociclib.Approved
PaliperidoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Paliperidone.Approved
PantoprazoleThe metabolism of Troglitazone can be decreased when combined with Pantoprazole.Approved
PasireotideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Pasireotide.Approved
PentamidineThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Pentamidine.Approved
PentobarbitalThe metabolism of Troglitazone can be increased when combined with Pentobarbital.Approved, Vet Approved
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Troglitazone.Approved, Investigational, Vet Approved, Withdrawn
PhenobarbitalThe metabolism of Troglitazone can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Troglitazone can be increased when combined with Phenytoin.Approved, Vet Approved
PioglitazoneThe metabolism of Troglitazone can be decreased when combined with Pioglitazone.Approved, Investigational
PiperazineThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Piperazine.Approved, Vet Approved
PipotiazineThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Pipotiazine.Approved, Investigational
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Troglitazone.Approved
PolythiazideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Polythiazide.Approved
PosaconazoleThe metabolism of Troglitazone can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Troglitazone.Approved
PrednisoloneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Prednisolone.Approved, Vet Approved
PrednisoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Prednisone.Approved, Vet Approved
PregabalinPregabalin may increase the fluid retaining activities of Troglitazone.Approved, Illicit, Investigational
PrimidoneThe metabolism of Troglitazone can be increased when combined with Primidone.Approved, Vet Approved
ProgesteroneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Progesterone.Approved, Vet Approved
PyrimethamineThe metabolism of Troglitazone can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuetiapineThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Quetiapine.Approved
QuinethazoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Quinethazone.Approved
QuinineThe metabolism of Troglitazone can be decreased when combined with Quinine.Approved
RabeprazoleThe metabolism of Troglitazone can be decreased when combined with Rabeprazole.Approved, Investigational
RanolazineThe metabolism of Troglitazone can be decreased when combined with Ranolazine.Approved, Investigational
RepaglinideTroglitazone may increase the hypoglycemic activities of Repaglinide.Approved, Investigational
RifabutinThe metabolism of Troglitazone can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Troglitazone can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Troglitazone can be increased when combined with Rifapentine.Approved
RilpivirineThe serum concentration of Rilpivirine can be decreased when it is combined with Troglitazone.Approved
RisperidoneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Risperidone.Approved, Investigational
RitonavirThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Ritonavir.Approved, Investigational
RosiglitazoneThe metabolism of Troglitazone can be decreased when combined with Rosiglitazone.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Troglitazone.Approved
SaquinavirThe metabolism of Troglitazone can be decreased when combined with Saquinavir.Approved, Investigational
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Troglitazone.Approved
SecobarbitalThe metabolism of Troglitazone can be increased when combined with Secobarbital.Approved, Vet Approved
SertralineThe metabolism of Troglitazone can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Troglitazone can be decreased when combined with Sildenafil.Approved, Investigational
SiltuximabThe serum concentration of Troglitazone can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Troglitazone can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Troglitazone.Approved
SirolimusThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Sirolimus.Approved, Investigational
SorafenibThe metabolism of Troglitazone can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Troglitazone can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Troglitazone can be increased when it is combined with Stiripentol.Approved
SulfadiazineThe metabolism of Troglitazone can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Troglitazone can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Troglitazone can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
SunitinibTroglitazone may increase the hypoglycemic activities of Sunitinib.Approved, Investigational
TacrolimusThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Tacrolimus.Approved, Investigational
TamoxifenThe metabolism of Troglitazone can be decreased when combined with Tamoxifen.Approved
TelaprevirThe metabolism of Troglitazone can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Troglitazone can be decreased when combined with Telithromycin.Approved
TemsirolimusThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Temsirolimus.Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Troglitazone.Experimental
TeriflunomideThe metabolism of Troglitazone can be decreased when combined with Teriflunomide.Approved
TicagrelorThe metabolism of Troglitazone can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Troglitazone can be decreased when combined with Ticlopidine.Approved
TipranavirThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Troglitazone can be decreased when it is combined with Tocilizumab.Approved
TolazamideTroglitazone may increase the hypoglycemic activities of Tolazamide.Approved
TolbutamideThe metabolism of Troglitazone can be decreased when combined with Tolbutamide.Approved
TopiramateThe metabolism of Troglitazone can be decreased when combined with Topiramate.Approved
TopiroxostatThe metabolism of Troglitazone can be decreased when combined with Topiroxostat.Approved, Investigational
TorasemideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Torasemide.Approved
TranylcypromineThe metabolism of Troglitazone can be decreased when combined with Tranylcypromine.Approved
TriamcinoloneThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Triamcinolone.Approved, Vet Approved
TrichlormethiazideThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Trichlormethiazide.Approved, Vet Approved
TrimethoprimThe metabolism of Troglitazone can be decreased when combined with Trimethoprim.Approved, Vet Approved
TriptorelinThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Triptorelin.Approved, Vet Approved
UbidecarenoneThe serum concentration of Ubidecarenone can be increased when it is combined with Troglitazone.Approved, Investigational, Nutraceutical
Valproic AcidThe metabolism of Troglitazone can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Troglitazone can be decreased when combined with Valsartan.Approved, Investigational
VenlafaxineThe metabolism of Troglitazone can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Troglitazone can be decreased when combined with Verapamil.Approved
VoriconazoleThe metabolism of Troglitazone can be decreased when combined with Voriconazole.Approved, Investigational
VorinostatThe therapeutic efficacy of Troglitazone can be decreased when used in combination with Vorinostat.Approved, Investigational
ZafirlukastThe metabolism of Troglitazone can be decreased when combined with Zafirlukast.Approved, Investigational
ZiprasidoneThe metabolism of Troglitazone can be decreased when combined with Ziprasidone.Approved
ZucapsaicinThe metabolism of Troglitazone can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

References

Synthesis Reference

Krishnamurthi Vyas, Chebiyyam Prabhakar, Sreenivas Dharmaraja Rao, Mamillapalli Ramabadhra Sarma, Om Gaddam Reddy, Rajagopalan Ramanujam, Ranjan Chakrabarti, "Polymorphic forms of troglitazone having enhanced anti-diabetic activity and a process for their preparation." U.S. Patent US5700820, issued June, 1992.

US5700820
General References
  1. Aljada A, Garg R, Ghanim H, Mohanty P, Hamouda W, Assian E, Dandona P: Nuclear factor-kappaB suppressive and inhibitor-kappaB stimulatory effects of troglitazone in obese patients with type 2 diabetes: evidence of an antiinflammatory action? J Clin Endocrinol Metab. 2001 Jul;86(7):3250-6. [PubMed:11443197]
External Links
KEGG Drug
D00395
PubChem Compound
5591
PubChem Substance
46504655
ChemSpider
5389
ChEBI
9753
ChEMBL
CHEMBL408
Therapeutic Targets Database
DAP001337
PharmGKB
PA451799
IUPHAR
2693
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Troglitazone
ATC Codes
A10BG01 — Troglitazone
FDA label
Download (501 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentImpaired Glucose Tolerance (IGT) / Type 2 Diabetes Mellitus1
2CompletedTreatmentSarcomas1
2, 3CompletedTreatmentAtherosclerosis / Diabetes Mellitus (DM)1
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus3

Pharmacoeconomics

Manufacturers
  • Sankyo usa corp
  • Pfizer pharmaceuticals ltd
Packagers
Dosage forms
Not Available
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5602133No1993-09-152013-09-15Us
US5859037No1997-11-132017-11-13Us
US6011049No1997-11-132017-11-13Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)184-186 °CNot Available
logP3.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00121 mg/mLALOGPS
logP4.16ALOGPS
logP5.5ChemAxon
logS-5.6ALOGPS
pKa (Strongest Acidic)6.61ChemAxon
pKa (Strongest Basic)-4.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area84.86 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity120.99 m3·mol-1ChemAxon
Polarizability47.08 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.868
Blood Brain Barrier+0.8183
Caco-2 permeable-0.6915
P-glycoprotein substrateSubstrate0.7514
P-glycoprotein inhibitor INon-inhibitor0.7854
P-glycoprotein inhibitor IINon-inhibitor0.7015
Renal organic cation transporterNon-inhibitor0.861
CYP450 2C9 substrateNon-substrate0.8329
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.7408
CYP450 1A2 substrateNon-inhibitor0.5726
CYP450 2C9 inhibitorNon-inhibitor0.6843
CYP450 2D6 inhibitorNon-inhibitor0.9266
CYP450 2C19 inhibitorNon-inhibitor0.6359
CYP450 3A4 inhibitorNon-inhibitor0.5517
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5121
Ames testNon AMES toxic0.584
CarcinogenicityNon-carcinogens0.9211
BiodegradationNot ready biodegradable0.9881
Rat acute toxicity1.9768 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9911
hERG inhibition (predictor II)Non-inhibitor0.6643
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as 1-benzopyrans. These are organic aromatic compounds that 1-benzopyran, a bicyclic compound made up of a benzene ring fused to a pyran, so that the oxygen atom is at the 1-position.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzopyrans
Sub Class
1-benzopyrans
Direct Parent
1-benzopyrans
Alternative Parents
Phenoxy compounds / Phenol ethers / Thiazolidinediones / Alkyl aryl ethers / Dicarboximides / Thiocarbamic acid derivatives / Organic carbonic acids and derivatives / Oxacyclic compounds / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
1-benzopyran / Phenoxy compound / Phenol ether / Alkyl aryl ether / Thiazolidinedione / Monocyclic benzene moiety / Benzenoid / Dicarboximide / Thiazolidine / Carbonic acid derivative
show 14 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
thiazolidinone, chromanes (CHEBI:9753) / a small molecule (CPD-11439)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
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...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
References
  1. Kitamura S, Miyazaki Y, Shinomura Y, Kondo S, Kanayama S, Matsuzawa Y: Peroxisome proliferator-activated receptor gamma induces growth arrest and differentiation markers of human colon cancer cells. Jpn J Cancer Res. 1999 Jan;90(1):75-80. [PubMed:10076568]
  2. Demetri GD, Fletcher CD, Mueller E, Sarraf P, Naujoks R, Campbell N, Spiegelman BM, Singer S: Induction of solid tumor differentiation by the peroxisome proliferator-activated receptor-gamma ligand troglitazone in patients with liposarcoma. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3951-6. [PubMed:10097144]
  3. Petrova TV, Akama KT, Van Eldik LJ: Cyclopentenone prostaglandins suppress activation of microglia: down-regulation of inducible nitric-oxide synthase by 15-deoxy-Delta12,14-prostaglandin J2. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4668-73. [PubMed:10200320]
  4. Camp HS, Whitton AL, Tafuri SR: PPARgamma activators down-regulate the expression of PPARgamma in 3T3-L1 adipocytes. FEBS Lett. 1999 Mar 26;447(2-3):186-90. [PubMed:10214942]
  5. Satoh T, Furuta K, Suzuki M, Watanabe Y: Prostaglandin J2 and its metabolites promote neurite outgrowth induced by nerve growth factor in PC12 cells. Biochem Biophys Res Commun. 1999 Apr 29;258(1):50-3. [PubMed:10222233]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Baek SJ, Wilson LC, Hsi LC, Eling TE: Troglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma ) ligand, selectively induces the early growth response-1 gene independently of PPAR gamma. A novel mechanism for its anti-tumorigenic activity. J Biol Chem. 2003 Feb 21;278(8):5845-53. Epub 2002 Dec 9. [PubMed:12475986]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Very long-chain fatty acid-coa ligase activity
Specific Function
Activation of long-chain fatty acids for both synthesis of cellular lipids, and degradation via beta-oxidation. Preferentially uses arachidonate and eicosapentaenoate as substrates.
Gene Name
ACSL4
Uniprot ID
O60488
Uniprot Name
Long-chain-fatty-acid--CoA ligase 4
Molecular Weight
79187.38 Da
References
  1. Kim JH, Lewin TM, Coleman RA: Expression and characterization of recombinant rat Acyl-CoA synthetases 1, 4, and 5. Selective inhibition by triacsin C and thiazolidinediones. J Biol Chem. 2001 Jul 6;276(27):24667-73. Epub 2001 Apr 23. [PubMed:11319222]
  2. Lewin TM, Van Horn CG, Krisans SK, Coleman RA: Rat liver acyl-CoA synthetase 4 is a peripheral-membrane protein located in two distinct subcellular organelles, peroxisomes, and mitochondrial-associated membrane. Arch Biochem Biophys. 2002 Aug 15;404(2):263-70. [PubMed:12147264]
  3. Lewin TM, Kim JH, Granger DA, Vance JE, Coleman RA: Acyl-CoA synthetase isoforms 1, 4, and 5 are present in different subcellular membranes in rat liver and can be inhibited independently. J Biol Chem. 2001 Jul 6;276(27):24674-9. Epub 2001 Apr 23. [PubMed:11319232]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Serine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. Its rapid interaction with PLAT may function as a major con...
Gene Name
SERPINE1
Uniprot ID
P05121
Uniprot Name
Plasminogen activator inhibitor 1
Molecular Weight
45059.695 Da
References
  1. Sobel BE: Insulin resistance and thrombosis: a cardiologist's view. Am J Cardiol. 1999 Jul 8;84(1A):37J-41J. [PubMed:10418858]
  2. Gottschling-Zeller H, Rohrig K, Hauner H: Troglitazone reduces plasminogen activator inhibitor-1 expression and secretion in cultured human adipocytes. Diabetologia. 2000 Mar;43(3):377-83. [PubMed:10768100]
  3. Nordt TK, Peter K, Bode C, Sobel BE: Differential regulation by troglitazone of plasminogen activator inhibitor type 1 in human hepatic and vascular cells. J Clin Endocrinol Metab. 2000 Apr;85(4):1563-8. [PubMed:10770198]
  4. Kato K, Yamada D, Midorikawa S, Sato W, Watanabe T: Improvement by the insulin-sensitizing agent, troglitazone, of abnormal fibrinolysis in type 2 diabetes mellitus. Metabolism. 2000 May;49(5):662-5. [PubMed:10831180]
  5. Kruszynska YT, Yu JG, Olefsky JM, Sobel BE: Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and in lean and obese normal subjects. Diabetes. 2000 Apr;49(4):633-9. [PubMed:10871202]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Nucleoside transmembrane transporter activity
Specific Function
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR...
Gene Name
SLC29A1
Uniprot ID
Q99808
Uniprot Name
Equilibrative nucleoside transporter 1
Molecular Weight
50218.805 Da
References
  1. Leung GP, Man RY, Tse CM: Effect of thiazolidinediones on equilibrative nucleoside transporter-1 in human aortic smooth muscle cells. Biochem Pharmacol. 2005 Aug 1;70(3):355-62. [PubMed:15963471]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inverse agonist
General Function
Zinc ion binding
Specific Function
Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response ...
Gene Name
ESRRG
Uniprot ID
P62508
Uniprot Name
Estrogen-related receptor gamma
Molecular Weight
51305.485 Da
References
  1. Wang Y, Fang F, Wong CW: Troglitazone is an estrogen-related receptor alpha and gamma inverse agonist. Biochem Pharmacol. 2010 Jul 1;80(1):80-5. doi: 10.1016/j.bcp.2010.03.013. Epub 2010 Mar 16. [PubMed:20298676]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inverse agonist
General Function
Zinc ion binding
Specific Function
Binds to an ERR-alpha response element (ERRE) containing a single consensus half-site, 5'-TNAAGGTCA-3'. Can bind to the medium-chain acyl coenzyme A dehydrogenase (MCAD) response element NRRE-1 and...
Gene Name
ESRRA
Uniprot ID
P11474
Uniprot Name
Steroid hormone receptor ERR1
Molecular Weight
45509.11 Da
References
  1. Wang Y, Fang F, Wong CW: Troglitazone is an estrogen-related receptor alpha and gamma inverse agonist. Biochem Pharmacol. 2010 Jul 1;80(1):80-5. doi: 10.1016/j.bcp.2010.03.013. Epub 2010 Mar 16. [PubMed:20298676]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-lin...
Gene Name
PPARD
Uniprot ID
Q03181
Uniprot Name
Peroxisome proliferator-activated receptor delta
Molecular Weight
49902.99 Da
References
  1. Inoue I, Itoh F, Aoyagi S, Tazawa S, Kusama H, Akahane M, Mastunaga T, Hayashi K, Awata T, Komoda T, Katayama S: Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem Biophys Res Commun. 2002 Jan 11;290(1):131-9. [PubMed:11779144]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
Gene Name
PPARA
Uniprot ID
Q07869
Uniprot Name
Peroxisome proliferator-activated receptor alpha
Molecular Weight
52224.595 Da
References
  1. Inoue I, Itoh F, Aoyagi S, Tazawa S, Kusama H, Akahane M, Mastunaga T, Hayashi K, Awata T, Komoda T, Katayama S: Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. Biochem Biophys Res Commun. 2002 Jan 11;290(1):131-9. [PubMed:11779144]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
S-nitrosoglutathione binding
Specific Function
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
Gene Name
GSTP1
Uniprot ID
P09211
Uniprot Name
Glutathione S-transferase P
Molecular Weight
23355.625 Da
References
  1. Boerma JS, Vermeulen NP, Commandeur JN: Application of CYP102A1M11H as a tool for the generation of protein adducts of reactive drug metabolites. Chem Res Toxicol. 2011 Aug 15;24(8):1263-74. doi: 10.1021/tx2001515. Epub 2011 Jun 16. [PubMed:21639118]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid binding
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A1
Uniprot ID
P22309
Uniprot Name
UDP-glucuronosyltransferase 1-1
Molecular Weight
59590.91 Da
References
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. [PubMed:12433820]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Schoch GA, Yano JK, Sansen S, Dansette PM, Stout CD, Johnson EF: Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid. J Biol Chem. 2008 Jun 20;283(25):17227-37. doi: 10.1074/jbc.M802180200. Epub 2008 Apr 15. [PubMed:18413310]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inducer
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
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 reg...
Gene Name
UGT1A3
Uniprot ID
P35503
Uniprot Name
UDP-glucuronosyltransferase 1-3
Molecular Weight
60337.835 Da
References
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. [PubMed:12433820]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
Gene Name
UGT1A4
Uniprot ID
P22310
Uniprot Name
UDP-glucuronosyltransferase 1-4
Molecular Weight
60024.535 Da
References
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. [PubMed:12433820]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Protein homodimerization activity
Specific Function
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 3 lacks trans...
Gene Name
UGT1A6
Uniprot ID
P19224
Uniprot Name
UDP-glucuronosyltransferase 1-6
Molecular Weight
60750.215 Da
References
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. [PubMed:12433820]
  2. Ito M, Yamamoto K, Sato H, Fujiyama Y, Bamba T: Inhibitory effect of troglitazone on glucuronidation catalyzed by human uridine diphosphate-glucuronosyltransferase 1A6. Eur J Clin Pharmacol. 2001 Mar;56(12):893-5. [PubMed:11317477]
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 reg...
Gene Name
UGT1A7
Uniprot ID
Q9HAW7
Uniprot Name
UDP-glucuronosyltransferase 1-7
Molecular Weight
59818.315 Da
References
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. [PubMed:12433820]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid 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 reg...
Gene Name
UGT1A8
Uniprot ID
Q9HAW9
Uniprot Name
UDP-glucuronosyltransferase 1-8
Molecular Weight
59741.035 Da
References
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. [PubMed:12433820]
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. This isoform has specificity for phenols. Isoform 2 lacks trans...
Gene Name
UGT1A9
Uniprot ID
O60656
Uniprot Name
UDP-glucuronosyltransferase 1-9
Molecular Weight
59940.495 Da
References
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. [PubMed:12433820]
  2. Barbier O, Villeneuve L, Bocher V, Fontaine C, Torra IP, Duhem C, Kosykh V, Fruchart JC, Guillemette C, Staels B: The UDP-glucuronosyltransferase 1A9 enzyme is a peroxisome proliferator-activated receptor alpha and gamma target gene. J Biol Chem. 2003 Apr 18;278(16):13975-83. Epub 2003 Feb 11. [PubMed:12582161]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Protein kinase c 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 reg...
Gene Name
UGT1A10
Uniprot ID
Q9HAW8
Uniprot Name
UDP-glucuronosyltransferase 1-10
Molecular Weight
59809.075 Da
References
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. [PubMed:12433820]
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 su...
Gene Name
UGT2B7
Uniprot ID
P16662
Uniprot Name
UDP-glucuronosyltransferase 2B7
Molecular Weight
60694.12 Da
References
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. [PubMed:12433820]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Glucuronosyltransferase activity
Specific Function
UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme displays activity toward several classes of xeno...
Gene Name
UGT2B15
Uniprot ID
P54855
Uniprot Name
UDP-glucuronosyltransferase 2B15
Molecular Weight
61035.815 Da
References
  1. Watanabe Y, Nakajima M, Yokoi T: Troglitazone glucuronidation in human liver and intestine microsomes: high catalytic activity of UGT1A8 and UGT1A10. Drug Metab Dispos. 2002 Dec;30(12):1462-9. [PubMed:12433820]

Transporters

Details
1. Bile salt export pump
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [PubMed:12739759]
  2. Funk C, Pantze M, Jehle L, Ponelle C, Scheuermann G, Lazendic M, Gasser R: Troglitazone-induced intrahepatic cholestasis by an interference with the hepatobiliary export of bile acids in male and female rats. Correlation with the gender difference in troglitazone sulfate formation and the inhibition of the canalicular bile salt export pump (Bsep) by troglitazone and troglitazone sulfate. Toxicology. 2001 Oct 5;167(1):83-98. [PubMed:11557132]
  3. Saito H, Osumi M, Hirano H, Shin W, Nakamura R, Ishikawa T: Technical pitfalls and improvements for high-speed screening and QSAR analysis to predict inhibitors of the human bile salt export pump (ABCB11/BSEP). AAPS J. 2009 Sep;11(3):581-9. doi: 10.1208/s12248-009-9137-9. Epub 2009 Aug 18. [PubMed:19688600]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
Gene Name
SLCO1B1
Uniprot ID
Q9Y6L6
Uniprot Name
Solute carrier organic anion transporter family member 1B1
Molecular Weight
76447.99 Da
References
  1. Nozawa T, Sugiura S, Nakajima M, Goto A, Yokoi T, Nezu J, Tsuji A, Tamai I: Involvement of organic anion transporting polypeptides in the transport of troglitazone sulfate: implications for understanding troglitazone hepatotoxicity. Drug Metab Dispos. 2004 Mar;32(3):291-4. [PubMed:14977862]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 14:25