Identification

Name
Pioglitazone
Accession Number
DB01132  (APRD00653)
Type
Small Molecule
Groups
Approved, Investigational
Description

Pioglitazone is a medication belonging to the thiazolidinedione class of drugs that are used as adjuncts to diet, exercise, and other diabetes medications to manage type 2 diabetes mellitus. The thiazolidinedione class of medications exerts its pharmacological effect primarily by promoting insulin sensitivity and the improved uptake of blood glucose. Following entry into fat cell nuclei, pioglitazone selectively binds to the Peroxisome Proliferator-Activated Receptor Gamma (PPARγ)[4]. PPARs are ligand-activated transcription factors that are involved in the expression of more than 100 genes, and affect numerous metabolic processes, notably lipid and glucose homeostasis [5]. PPARγ in particular is abundantly expressed in lipid cells (adipocytes), where it plays a central role in lipid production and regulation of lipid metabolism.

Structure
Thumb
Synonyms
  • (+-)-5-((4-(2-(5-Ethyl-2-pyridinyl)ethoxy)phenyl)methyl)-2,4-thiazolidinedione
  • 5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1,3-thiazolidine-2,4-dione
  • Pioglitazona
  • Pioglitazone
  • Pioglitazonum
External IDs
U 72107A / U-72107A / U72107A
Product Ingredients
IngredientUNIICASInChI Key
Pioglitazone HydrochlorideJQT35NPK6C112529-15-4GHUUBYQTCDQWRA-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel PioglitazoneTablet15 mgOralAccel Pharma Inc2009-06-02Not applicableCanada
Accel PioglitazoneTablet45 mgOralAccel Pharma Inc2009-06-02Not applicableCanada
Accel PioglitazoneTablet30 mgOralAccel Pharma Inc2009-06-02Not applicableCanada
Act PioglitazoneTablet45 mgOralActavis Pharma Company2007-12-05Not applicableCanada
Act PioglitazoneTablet30 mgOralActavis Pharma Company2007-12-05Not applicableCanada
Act PioglitazoneTablet15 mgOralActavis Pharma Company2007-12-05Not applicableCanada
ActosTablet15 mgOralTakeda Pharma A/S2000-10-13Not applicableEu
ActosTablet30 mg/1Occlusive dressing techniqueDispensing Solutions, Inc.1999-07-15Not applicableUs
ActosTablet30 mgOralTakeda Pharma A/S2000-10-13Not applicableEu
ActosTablet45 mg/1OralTakeda1999-07-15Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ach-pioglitazoneTablet45 mgOralAccord Healthcare Limited2010-06-11Not applicableCanada
Ach-pioglitazoneTablet30 mgOralAccord Healthcare Limited2010-06-11Not applicableCanada
Ach-pioglitazoneTablet15 mgOralAccord Healthcare Limited2012-10-12Not applicableCanada
Ag-pioglitazoneTablet30 mgOralAngita Pharma Inc.Not applicableNot applicableCanada
Ag-pioglitazoneTablet45 mgOralAngita Pharma Inc.Not applicableNot applicableCanada
Apo-pioglitazoneTablet45 mgOralApotex Corporation2007-12-05Not applicableCanada
Apo-pioglitazoneTablet30 mgOralApotex Corporation2007-12-05Not applicableCanada
Apo-pioglitazoneTablet15 mgOralApotex Corporation2007-12-05Not applicableCanada
Auro-pioglitazoneTablet45 mgOralAuro Pharma Inc2012-07-24Not applicableCanada
Auro-pioglitazoneTablet30 mgOralAuro Pharma Inc2012-07-24Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Actoplus MetPioglitazone Hydrochloride (15 mg/1) + Metformin Hydrochloride (850 mg/1)Tablet, film coatedOralTakeda2005-08-29Not applicableUs
Actoplus MetPioglitazone Hydrochloride (15 mg/1) + Metformin Hydrochloride (850 mg/1)Tablet, film coatedOralCardinal Health2005-08-292014-05-31Us
Actoplus MetPioglitazone Hydrochloride (15 mg/1) + Metformin Hydrochloride (850 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2006-03-21Not applicableUs
Actoplus MetPioglitazone Hydrochloride (15 mg/1) + Metformin Hydrochloride (500 mg/1)Tablet, film coatedOralTakeda2005-08-29Not applicableUs
Actoplus MetPioglitazone Hydrochloride (15 mg/1) + Metformin Hydrochloride (500 mg/1)Tablet, film coatedOralPhysicians Total Care, Inc.2006-01-04Not applicableUs
Actoplus Met XRPioglitazone Hydrochloride (30 mg/1) + Metformin Hydrochloride (1000 mg/1)Tablet, film coated, extended releaseOralTakeda2010-06-11Not applicableUs
Actoplus Met XRPioglitazone Hydrochloride (15 mg/1) + Metformin Hydrochloride (1000 mg/1)Tablet, film coated, extended releaseOralTakeda2010-06-11Not applicableUs
Alogliptin and PioglitazonePioglitazone Hydrochloride (15 mg/1) + Alogliptin benzoate (25 mg/1)Tablet, film coatedOralPerrigo New York Inc.2016-04-08Not applicableUs
Alogliptin and PioglitazonePioglitazone Hydrochloride (15 mg/1) + Alogliptin benzoate (12.5 mg/1)Tablet, film coatedOralPerrigo New York Inc.2016-04-08Not applicableUs
Alogliptin and PioglitazonePioglitazone Hydrochloride (30 mg/1) + Alogliptin benzoate (25 mg/1)Tablet, film coatedOralPerrigo New York Inc.2016-04-08Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
PaglitazPioglitazone Hydrochloride (45 mg)TabletOralKrka, D.D., Novo Mesto2012-03-212016-03-10Eu
PaglitazPioglitazone Hydrochloride (15 mg)TabletOralKrka, D.D., Novo Mesto2012-03-212016-03-10Eu
PaglitazPioglitazone Hydrochloride (15 mg)TabletOralKrka, D.D., Novo Mesto2012-03-212016-03-10Eu
PaglitazPioglitazone Hydrochloride (30 mg)TabletOralKrka, D.D., Novo Mesto2012-03-212016-03-10Eu
PaglitazPioglitazone Hydrochloride (30 mg)TabletOralKrka, D.D., Novo Mesto2012-03-212016-03-10Eu
PaglitazPioglitazone Hydrochloride (30 mg)TabletOralKrka, D.D., Novo Mesto2012-03-212016-03-10Eu
PaglitazPioglitazone Hydrochloride (15 mg)TabletOralKrka, D.D., Novo Mesto2012-03-212016-03-10Eu
PaglitazPioglitazone Hydrochloride (45 mg)TabletOralKrka, D.D., Novo Mesto2012-03-212016-03-10Eu
PaglitazPioglitazone Hydrochloride (15 mg)TabletOralKrka, D.D., Novo Mesto2012-03-212016-03-10Eu
PaglitazPioglitazone Hydrochloride (45 mg)TabletOralKrka, D.D., Novo Mesto2012-03-212016-03-10Eu
International/Other Brands
Actost / Glustin
Categories
UNII
X4OV71U42S
CAS number
111025-46-8
Weight
Average: 356.439
Monoisotopic: 356.119463206
Chemical Formula
C19H20N2O3S
InChI Key
HYAFETHFCAUJAY-UHFFFAOYSA-N
InChI
InChI=1S/C19H20N2O3S/c1-2-13-3-6-15(20-12-13)9-10-24-16-7-4-14(5-8-16)11-17-18(22)21-19(23)25-17/h3-8,12,17H,2,9-11H2,1H3,(H,21,22,23)
IUPAC Name
5-({4-[2-(5-ethylpyridin-2-yl)ethoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione
SMILES
CCC1=CN=C(CCOC2=CC=C(CC3SC(=O)NC3=O)C=C2)C=C1

Pharmacology

Indication

Pioglitazone is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus [Label].

Associated Conditions
Pharmacodynamics

Pioglitazone enhances cellular responsiveness to insulin, increases insulin-dependent glucose disposal and improves hepatic sensitivity to insulin. In patients with type 2 diabetes, the decreased insulin resistance produced by pioglitazone results in lower plasma glucose concentrations, lower plasma insulin concentrations, and lower HbA1c values [Label]

Additionally, patients treated with pioglitazone had mean decreases in serum triglycerides, mean increases in HDL cholesterol, and no consistent mean changes in LDL and total cholesterol [Label].

Mechanism of action

Pioglitazone acts as a selective agonist at Peroxisome Proliferator Activated Receptor Gamma (PPARγ) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR-gamma receptors increases the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In this way, pioglitazone both enhances tissue sensitivity to insulin and reduces the production of glucose via the liver (hepatic gluconeogenesis). Thus, insulin resistance associated with type 2 diabetes mellitus is improved without an increase in insulin secretion by pancreatic β cells.

TargetActionsOrganism
APeroxisome proliferator-activated receptor gamma
agonist
Human
UPeroxisome proliferator-activated receptor deltaNot AvailableHuman
UPeroxisome proliferator-activated receptor alphaNot AvailableHuman
UAmine oxidase [flavin-containing] BNot AvailableHuman
Absorption

Following oral administration of pioglitazone, peak concentrations of pioglitazone were observed within 2 hours. Food slightly delays the time to peak serum concentration (T max) to 3 to 4 hours, but does not alter the extent of absorption (AUC). Steady state concentrations are achieved after 7 days of once daily administration of pioglitazone [Label].

Volume of distribution

0.63 ± 0.41 L/kg [Label]

Protein binding

Pioglitazone is extensively protein bound (> 99%) in human serum, principally to serum albumin. Pioglitazone also binds to other serum proteins, but with lower affinity [Label].

Metabolism

Pioglitazone is extensively metabolized by hydroxylation and oxidation; the metabolites also partly convert to glucuronide or sulfate conjugates. Metabolites M-III and M-IV are the major circulating active metabolites in humans. The cytochrome P450 isoforms involved are CYP2C8 and, to a lesser degree, CYP3A4 with additional contributions from a variety of other isoforms including the mainly extrahepatic CYP1A1 [Label].

Route of elimination

Following oral administration, approximately 15% to 30% of the pioglitazone dose is recovered in the urine. Renal elimination of pioglitazone is negligible, and the drug is excreted primarily as metabolites and their conjugates. It is presumed that most of the oral dose is excreted into the bile either unchanged or as metabolites and eliminated in the feces [Label].

Half life

The mean serum half-life of pioglitazone and its metabolites (M-III and M-IV) range from 3 to 7 hours and 16 to 24 hours, respectively [Label].

Clearance

The apparent clearance of orally administered pioglitazone is 5 - 7 L/h [Label].

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Pioglitazone.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Pioglitazone.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Pioglitazone is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Pioglitazone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Pioglitazone.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Pioglitazone can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Pioglitazone.
6-Deoxyerythronolide BThe metabolism of Pioglitazone can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be increased when combined with Pioglitazone.
AbemaciclibThe metabolism of Abemaciclib can be increased when combined with Pioglitazone.
Food Interactions
  • Take without regard to meals. Food slightly delays absorption rate but extent of absorption is not affected.

References

Synthesis Reference

Chandra Khanduri, Yatendra Kumar, Atulya Panda, Suchitra Chakraborty, Mukesh Sharma, "Process for the preparation of pioglitazone." U.S. Patent US20070078170, issued April 05, 2007.

US20070078170
General References
  1. Colca JR, McDonald WG, Waldon DJ, Leone JW, Lull JM, Bannow CA, Lund ET, Mathews WR: Identification of a novel mitochondrial protein ("mitoNEET") cross-linked specifically by a thiazolidinedione photoprobe. Am J Physiol Endocrinol Metab. 2004 Feb;286(2):E252-60. Epub 2003 Oct 21. [PubMed:14570702]
  2. Paddock ML, Wiley SE, Axelrod HL, Cohen AE, Roy M, Abresch EC, Capraro D, Murphy AN, Nechushtai R, Dixon JE, Jennings PA: MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14342-7. Epub 2007 Aug 31. [PubMed:17766440]
  3. Lincoff AM, Wolski K, Nicholls SJ, Nissen SE: Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. JAMA. 2007 Sep 12;298(10):1180-8. [PubMed:17848652]
  4. Al-Majed A, Bakheit AH, Abdel Aziz HA, Alharbi H, Al-Jenoobi FI: Pioglitazone. Profiles Drug Subst Excip Relat Methodol. 2016;41:379-438. doi: 10.1016/bs.podrm.2015.11.002. Epub 2016 Feb 2. [PubMed:26940171]
  5. Janani C, Ranjitha Kumari BD: PPAR gamma gene--a review. Diabetes Metab Syndr. 2015 Jan-Mar;9(1):46-50. doi: 10.1016/j.dsx.2014.09.015. Epub 2014 Oct 13. [PubMed:25450819]
External Links
Human Metabolome Database
HMDB0015264
KEGG Compound
C07675
PubChem Compound
4829
PubChem Substance
46507136
ChemSpider
4663
ChEBI
8228
ChEMBL
CHEMBL595
Therapeutic Targets Database
DAP000272
PharmGKB
PA450970
IUPHAR
2694
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Pioglitazone
ATC Codes
A10BD09 — Pioglitazone and alogliptinA10BD12 — Pioglitazone and sitagliptinA10BD05 — Metformin and pioglitazoneA10BD06 — Glimepiride and pioglitazoneA10BG03 — Pioglitazone
AHFS Codes
  • 68:20.28 — Thiazolidinediones
FDA label
Download (61.6 KB)
MSDS
Download (36.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceBMI >30 kg/m2 / Infertility, Female1
0CompletedBasic ScienceLung Inflammation1
0CompletedBasic SciencePeripheral Arterial Disease (PAD)1
0CompletedTreatmentPolycystic Ovarian Syndrome1
0CompletedTreatmentPolycystic Ovaries Syndrome1
0Not Yet RecruitingTreatmentPioglitazone1
0RecruitingBasic ScienceMetabolic Syndromes / Obese1
1Active Not RecruitingTreatmentProstatic Neoplasms, Castration-Resistant1
1CompletedNot AvailableHealthy Volunteers2
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of ASP19411
1CompletedNot AvailableType 2 Diabetes Mellitus1
1CompletedBasic ScienceAmount of Pioglitazone in Blood / Drug Drug Interaction (DDI) / Healthy Volunteers / Pharmacokinetics / Pioglitazone / Rheumatoid Arthritis1
1CompletedBasic ScienceHealthy Volunteers3
1CompletedOtherHealthy Volunteers2
1CompletedPreventionDiabetes Mellitus (DM)1
1CompletedSupportive CareAnaplastic Astrocytoma (AA) / Brain Neoplasms, Benign / Brain Neoplasms, Malignant / Glioblastoma Multiforme (GBM) / Meningiomas malignant1
1CompletedTreatmentAdvanced Solid Tumors / Metastatic Solid Tumors1
1CompletedTreatmentAnemias1
1CompletedTreatmentBMI >27 kg/m2 / BMI >30 kg/m2 / Healthy Volunteers1
1CompletedTreatmentCastration Resistant Prostate Cancer (CRPC) / Pharmacokinetics of MDV31001
1CompletedTreatmentCrohn's Disease (CD)1
1CompletedTreatmentCystic Fibrosis (CF)1
1CompletedTreatmentDiabetes, Diabetes Mellitus Type 11
1CompletedTreatmentHealthy Volunteers8
1CompletedTreatmentNon-Alcoholic Fatty Liver Disease (NAFLD)1
1CompletedTreatmentRelapsing Remitting Multiple Sclerosis (RRMS)1
1CompletedTreatmentType 2 Diabetes Mellitus3
1Not Yet RecruitingBasic ScienceInclusion Body Myositis (IBM) / Muscle Inflammation / Muscular Diseases / Musculoskeletal Disorders / Nervous System Diseases / Neuromuscular Diseases1
1Not Yet RecruitingHealth Services ResearchType 2 Diabetes Mellitus1
1RecruitingBasic ScienceAutoimmune Pulmonary Alveolar Proteinosis1
1RecruitingTreatmentInsulin Resistance / Rheumatoid Arthritis1
1RecruitingTreatmentObese1
1TerminatedTreatmentOpioid-Related Disorders1
1Unknown StatusTreatmentMalignant Neoplasm of Pancreas1
1WithdrawnNot AvailableType 2 Diabetes Mellitus1
1, 2CompletedTreatmentAlcohol Use Disorder (AUD) / Cocaine Use Disorders1
1, 2CompletedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
1, 2CompletedTreatmentSevere Sepsis / Shock, Septic1
1, 2CompletedTreatmentType 2 Diabetes Mellitus1
1, 2RecruitingPreventionSystemic Lupus Erthematosus1
1, 2RecruitingTreatmentChronic Granulomatous Disease (CGD)1
1, 2RecruitingTreatmentDisseminated Sclerosis1
1, 2RecruitingTreatmentLeukemia, Myeloid, Chronic-Phase1
1, 2TerminatedBasic ScienceHeroin Dependence / Nicotine Dependence1
1, 2Unknown StatusTreatmentMultiple Myeloma (MM)1
2Active Not RecruitingPreventionEndobronchial Dysplasia / Lung Cancers1
2Active Not RecruitingTreatmentPolycystic Kidney Diseases1
2CompletedDiagnosticDiabetes Mellitus (DM) / Healthy Volunteers / Platelet Function1
2CompletedPreventionHead and Neck Carcinoma / Oral Leukoplakia1
2CompletedPreventionMild Cognitive Impairment (MCI)1
2CompletedTreatmentAirflow Obstruction / Airway Inflammation / Severe, Refractory Asthma1
2CompletedTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentAsthma Bronchial1
2CompletedTreatmentAutism Spectrum Conditions/Disorders1
2CompletedTreatmentBMI >30 kg/m21
2CompletedTreatmentCancer of the Pancreas1
2CompletedTreatmentCardiac Allograft Vasculopathy / Cardiac Transplant1
2CompletedTreatmentCardiovascular Disease (CVD)1
2CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection1
2CompletedTreatmentCoronary Artery Disease / Oxidative Stress / Type 2 Diabetes Mellitus1
2CompletedTreatmentDiabetes Mellitus (DM)3
2CompletedTreatmentDiabetes Mellitus (DM) / Glucose Metabolism Disorders / Type 2 Diabetes Mellitus1
2CompletedTreatmentDiabetes Mellitus (DM) / Insulin Resistance1
2CompletedTreatmentESRD1
2CompletedTreatmentFatty Liver / Nonalcoholic Steatohepatitis1
2CompletedTreatmentHIV-1 and Hepatitis C Co-Infection1
2CompletedTreatmentHepatic Steatosis / Human Immunodeficiency Virus (HIV) Infections / Insulin Resistance1
2CompletedTreatmentHepatitis1
2CompletedTreatmentHigh Blood Pressure (Hypertension) / Inflammatory Reaction1
2CompletedTreatmentImpaired Glucose Tolerance (IGT) / Transplantation, Kidney1
2CompletedTreatmentInsulin Resistance / Metabolic Syndromes / Type 2 Diabetes Mellitus1
2CompletedTreatmentInsulin Resistance / Normal or Mildly Abnormal Stool Fat Levels / Normal Stool Fat Levels / Pancreatitis, Chronic1
2CompletedTreatmentIntracerebral Hemorrhage1
2CompletedTreatmentLeukemia, Myeloid, Chronic-Phase1
2CompletedTreatmentMajor Depressive Disorder (MDD) / Metabolic Syndromes1
2CompletedTreatmentNonalcoholic Fatty Liver Disease1
2CompletedTreatmentOpioid Abuse1
2CompletedTreatmentParkinson's Disease (PD)1
2CompletedTreatmentProstate Cancer1
2CompletedTreatmentThyroid Cancers That Contain the PAX8-PPARgamma Fusion Gene1
2CompletedTreatmentType 2 Diabetes Mellitus16
2Enrolling by InvitationPreventionSquamous Cell Carcinoma of the Skin1
2Not Yet RecruitingTreatmentLeukemia, Myelogenous, Chronic, BCR-ABL Positive1
2RecruitingOtherChronic Myeloid Leukemia (CML)1
2RecruitingTreatmentAlcohol Dependence1
2RecruitingTreatmentChronic Myelogenous Leukemia, BCR-ABL1 Positive / Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive1
2RecruitingTreatmentChronic Myeloid Leukemia (CML)1
2RecruitingTreatmentDiabetes Mellitus Type 2 With Hyperglycemia1
2RecruitingTreatmentHepatitis1
2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC) / Non-squamous Cell Lung Cancer / Squamous Cell Carcinoma of Lung1
2RecruitingTreatmentNeoplasms, Oropharyngeal / Oral Cavity Neoplasm / Stage 0 Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 / Stage 0 Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7 / Stage I Oral Cavity Squamous Cell Carcinoma / Stage I Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 / Stage I Oropharyngeal Squamous Cell Carcinoma / Stage I Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7 / Stage II Oral Cavity Squamous Cell Carcinoma / Stage II Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 / Stage II Oropharyngeal Squamous Cell Carcinoma / Stage II Oropharyngeal Squamous Cell Carcinoma AJCC v6 and v7 / Stage III Oral Cavity Squamous Cell Carcinoma / Stage III Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 / Stage III Oropharyngeal Squamous Cell Carcinoma / Stage III Oropharyngeal Squamous Cell Carcinoma AJCC v7 / Stage IV Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 / Stage IV Oropharyngeal Squamous Cell Carcinoma AJCC v7 / Stage IVA Oral Cavity Squamous Cell Carcinoma / Stage IVA Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 / Stage IVA Oropharyngeal Squamous Cell Carcinoma / Stage IVA Oropharyngeal Squamous Cell Carcinoma AJCC v7 / Stage IVB Oral Cavity Squamous Cell Carcinoma / Stage IVB Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 / Stage IVB Oropharyngeal Squamous Cell Carcinoma / Stage IVB Oropharyngeal Squamous Cell Carcinoma AJCC v7 / Stage IVC Oral Cavity Squamous Cell Carcinoma / Stage IVC Oral Cavity Squamous Cell Carcinoma AJCC v6 and v7 / Stage IVC Oropharyngeal Squamous Cell Carcinoma / Stage IVC Oropharyngeal Squamous Cell Carcinoma AJCC v71
2TerminatedNot AvailableType 2 Diabetes Mellitus1
2TerminatedTreatmentAlcohol Dependence / Alcohol Drinking / Alcohol-Related Disorders / Stress1
2TerminatedTreatmentAmyotrophic Lateral Sclerosis (ALS)1
2TerminatedTreatmentAsthma Bronchial / BMI >30 kg/m21
2TerminatedTreatmentChronic Kidney Disease (CKD)1
2TerminatedTreatmentDiabetes Mellitus (DM)1
2TerminatedTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2TerminatedTreatmentNonalcoholic Steatohapatitis1
2TerminatedTreatmentOral Leukoplakia1
2TerminatedTreatmentStage IA Non-Small Cell Lung Carcinoma / Stage IB Non-Small Cell Lung Carcinoma / Stage IIA Non-Small Cell Lung Carcinoma / Stage IIB Non-Small Cell Lung Carcinoma / Stage IIIA Non-Small Cell Lung Cancer1
2TerminatedTreatmentStrokes1
2TerminatedTreatmentType 2 Diabetes Mellitus2
2Unknown StatusNot AvailableHepatitis C Viral Infection1
2Unknown StatusTreatmentPsoriasis1
2WithdrawnTreatmentAirflow Obstruction / Airway Hyperactivity / Airway Inflammation / Asthma Bronchial1
2WithdrawnTreatmentPressure Ulcers / Spinal Cord Injuries (SCI)1
2, 3CompletedTreatmentArterial Occlusive Diseases / Insulin Resistance / Intermittent Claudication1
2, 3CompletedTreatmentCoronary Artery Disease / Type 2 Diabetes Mellitus1
2, 3CompletedTreatmentMajor Depressive Disorder (MDD)1
2, 3CompletedTreatmentType 2 Diabetes Mellitus4
2, 3CompletedTreatmentMinor burns1
2, 3Not Yet RecruitingOtherInsulin Sensitivity1
2, 3WithdrawnDiagnosticEndometriosis1
3Active Not RecruitingTreatmentType 2 Diabetes Mellitus1
3CompletedBasic ScienceType 2 Diabetes Mellitus1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension) / High Cholesterol / Type 2 Diabetes Mellitus1
3CompletedPreventionImpaired Glucose Tolerance (IGT) / Type 2 Diabetes Mellitus1
3CompletedTreatmentDiabetes Mellitus (DM)13
3CompletedTreatmentDiabetes Mellitus (DM) / Dyslipidemias1
3CompletedTreatmentDiabetes Mellitus (DM) / Myocardial Infarction / Strokes1
3CompletedTreatmentDiabetes Mellitus (DM) / Proteinuria / Transplantation, Kidney1
3CompletedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus2
3CompletedTreatmentFriedreich's Ataxia1
3CompletedTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
3CompletedTreatmentLiver Diseases1
3CompletedTreatmentRheumatoid Arthritis1
3CompletedTreatmentType 2 Diabetes Mellitus36
3TerminatedTreatmentChronic Hepatitis C Virus (HCV) Infection / Insulin Resistance1
3TerminatedTreatmentDiabetes Mellitus (DM)1
3TerminatedTreatmentDiabetes Mellitus (DM) / Type 2 Diabetes Mellitus1
3TerminatedTreatmentHIV-Associated Lipodystrophy Syndrome / Human Immunodeficiency Virus (HIV) Infections1
3TerminatedTreatmentMild Cognitive Impairment Due to Alzheimer's Disease2
3TerminatedTreatmentType 2 Diabetes Mellitus4
3Unknown StatusTreatmentCoronary Artery Atherosclerosis / Coronary Artery Restenosis / Diabetes Mellitus (DM)1
3Unknown StatusTreatmentFatty Liver1
3Unknown StatusTreatmentMetabolic Syndromes1
4CompletedNot AvailableDiabetes Mellitus (DM)1
4CompletedNot AvailableDiabetic Nephropathies / Dyslipidemias / High Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedNot AvailableType 2 Diabetes Mellitus1
4CompletedBasic ScienceDiabetes Mellitus (DM)1
4CompletedBasic ScienceDiabetes Mellitus (DM) / Glucose Metabolism Disorders1
4CompletedBasic ScienceInsulin Resistance / Metabolic Syndromes / Pre-Diabetic1
4CompletedBasic ScienceType 2 Diabetes Mellitus2
4CompletedPreventionAdverse Effects / Coronary Artery Atherosclerosis / Insulin resistance syndrome1
4CompletedPreventionAngina Pectoris / Coronary Artery Disease / Percutaneous Coronary Intervention / Type 2 Diabetes Mellitus1
4CompletedPreventionDiabetes Mellitus (DM)1
4CompletedTreatmentAscites / Liver Cirrhosis / Portal Hypertension1
4CompletedTreatmentAtaxia-Telangiectasia1
4CompletedTreatmentBMI >30 kg/m2 / Overweight With Indications for Weight Loss1
4CompletedTreatmentBone Metabolism1
4CompletedTreatmentCardiovascular Disease (CVD) / Type 2 Diabetes Mellitus1
4CompletedTreatmentChronic Hepatitis C Virus (HCV) Infection2
4CompletedTreatmentCognitive Impairments / Diabetes Mellitus (DM) / Insulin Resistance / Schizophrenic Disorders1
4CompletedTreatmentCoronary Artery Stenosis / Diabetes Mellitus (DM)1
4CompletedTreatmentCoronary Heart Disease (CHD) / Type 2 Diabetes Mellitus1
4CompletedTreatmentDepression, Bipolar / Insulin Resistance / Metabolic Syndromes1
4CompletedTreatmentDiabetes Mellitus (DM)4
4CompletedTreatmentDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
4CompletedTreatmentDiabetes Mellitus (DM) / Livers1
4CompletedTreatmentDiabetic Stable Angina / Diabetic Unstable Angina1
4CompletedTreatmentEnd-Stage Renal Disease (ESRD)1
4CompletedTreatmentHealthy Volunteers / Impaired Glucose Tolerance (IGT) / Type 2 Diabetes Mellitus1
4CompletedTreatmentHepatitis C Viral Infection1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Insulin Resistance1
4CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Lipodystrophies1
4CompletedTreatmentInflammatory Reaction1
4CompletedTreatmentInsulin Resistance / Polycystic Ovaries Syndrome1
4CompletedTreatmentInsulin Resistance / Type 2 Diabetes Mellitus2
4CompletedTreatmentMetabolic Syndromes2
4CompletedTreatmentNonalcoholic Fatty Liver Disease / Nonalcoholic Steatohepatitis / Type 2 Diabetes Mellitus1
4CompletedTreatmentNonalcoholic Steatohepatitis2
4CompletedTreatmentPolycystic Ovaries Syndrome1
4CompletedTreatmentSecondary Drug Failure / Type 2 Diabetes Mellitus1
4CompletedTreatmentSystemic Lupus Erythematosus (SLE)1
4CompletedTreatmentType 2 Diabetes Mellitus13
4CompletedTreatmentType 2 Diabetes Mellitus / Vascular Diseases1
4Enrolling by InvitationTreatmentType 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentDiabetes Mellitus (DM) / Osteoporosis1
4Not Yet RecruitingTreatmentNAFLD - Nonalcoholic Fatty Liver Disease / Type2 Diabetes1
4RecruitingBasic ScienceChronic Kidney Disease (CKD)1
4RecruitingTreatmentType 2 Diabetes Mellitus8
4TerminatedPreventionDiabetes Mellitus (DM) / Myocardial Infarction1
4TerminatedTreatmentBipolar Disorder (BD) / Insulin Resistance1
4TerminatedTreatmentFatty Liver / Hepatitis C Viral Infection / Human Immunodeficiency Virus (HIV) / Liver Diseases / Steatosis1
4TerminatedTreatmentNonalcoholic Fatty Liver / Type 2 Diabetes Mellitus1
4TerminatedTreatmentObstructive Sleep Apnea (OSA) / Polycystic Ovaries Syndrome1
4TerminatedTreatmentPulmonary Hypertension (PH)1
4TerminatedTreatmentType 2 Diabetes Mellitus2
4Unknown StatusBasic ScienceType 2 Diabetes Mellitus1
4Unknown StatusTreatmentChronic Hepatitis C Virus (HCV) Infection1
4Unknown StatusTreatmentCoronary Artery Atherosclerosis / Coronary Heart Disease (CHD) / Inflammatory Reaction1
4Unknown StatusTreatmentDiabetes Mellitus (DM)1
4Unknown StatusTreatmentDiabetes Mellitus (DM) / Oxidative Stress1
4Unknown StatusTreatmentESRD1
4Unknown StatusTreatmentInsulin Resistance / Major Depressive Disorder (MDD)1
4Unknown StatusTreatmentType 2 Diabetes Mellitus2
4WithdrawnTreatmentBMI >30 kg/m2 / Insulin Resistance1
4WithdrawnTreatmentGlucose Metabolism Disorders1
4WithdrawnTreatmentType 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableAdipocytes / Adiponectin / Bone Density / Mesenchymal Stem Cells / Osteoblast / Osteocalcin1
Not AvailableCompletedNot AvailableBladder Cancers / Diabetes Mellitus (DM)1
Not AvailableCompletedNot AvailableChronic Hepatitis C Virus (HCV) Infection1
Not AvailableCompletedNot AvailableCongenital Adrenal Hyperplasia (CAH)1
Not AvailableCompletedNot AvailableDiabetes Mellitus, Type 2, Cancer1
Not AvailableCompletedNot AvailableKetoacidosis, Diabetic / Ketosis Prone Diabetes / Severe Hyperglycemia1
Not AvailableCompletedNot AvailableType 2 Diabetes Mellitus10
Not AvailableCompletedBasic ScienceBMI >30 kg/m2 / Insulin Resistance1
Not AvailableCompletedBasic ScienceBMI >30 kg/m2 / Metabolic Syndromes1
Not AvailableCompletedBasic ScienceBMI >30 kg/m2 / Sarcopenia1
Not AvailableCompletedBasic ScienceMetabolic Syndromes / Prediabetic State1
Not AvailableCompletedBasic ScienceRheumatoid Arthritis1
Not AvailableCompletedBasic ScienceType 2 Diabetes Mellitus5
Not AvailableCompletedDiagnosticCardiovascular Disease (CVD) / HIV Lipodystrophy / Human Immunodeficiency Virus (HIV) Infections / Insulin Resistance / The Metabolic Syndrome1
Not AvailableCompletedOtherAnti Inflammatory Non-Steroidal / Cystic Fibrosis (CF) / Neutrophils1
Not AvailableCompletedPreventionAtherosclerosis / Insulin Resistance / Transplantation, Kidney1
Not AvailableCompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / BMI >30 kg/m2 / Cardiovascular Disease (CVD) / Human Immunodeficiency Virus (HIV) / Human Immunodeficiency Virus (HIV) Infections / Lipodystrophies / Type 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentAtherosclerosis / Impaired Glucose Tolerance (IGT) / Type 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentBMI >30 kg/m2 / Type 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentCystic Fibrosis (CF)1
Not AvailableCompletedTreatmentDiabetes Mellitus (DM) / Endstage Renal Disease1
Not AvailableCompletedTreatmentDiabetic Nephropathies / Type 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentEnd Stage Renal Disease (ESRD) / Hemodialysis Treatment1
Not AvailableCompletedTreatmentHuman Growth Hormone Deficiency1
Not AvailableCompletedTreatmentHypertriglyceridemias / Inflammatory Reaction / Insulin Resistance / Peritoneal dialysis therapy / Pioglitazone1
Not AvailableCompletedTreatmentNewly Diagnosed / Type 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentType 2 Diabetes Mellitus3
Not AvailableRecruitingNot AvailableBladder Cancers1
Not AvailableRecruitingBasic ScienceUric Acid Kidney Stone Disease1
Not AvailableRecruitingOtherType 2 Diabetes Mellitus1
Not AvailableRecruitingTreatmentImpaired Fasting Glucose (IFG) / Impaired Glucose Tolerance (IGT) / Type 2 Diabetes Mellitus1
Not AvailableRecruitingTreatmentType 2 Diabetes Mellitus1
Not AvailableTerminatedNot AvailableDiabetes Mellitus (DM) / Hypogonadism / Inflammatory Reaction / Metabolic Syndromes1
Not AvailableTerminatedBasic ScienceFatty Liver1
Not AvailableTerminatedHealth Services ResearchPolycystic Ovaries Syndrome1
Not AvailableTerminatedPreventionPrediabetic State1
Not AvailableTerminatedTreatmentChronic Kidney Disease (CKD)1
Not AvailableTerminatedTreatmentType 2 Diabetes Mellitus1
Not AvailableUnknown StatusNot AvailableHuman Immunodeficiency Virus (HIV) Infections1
Not AvailableUnknown StatusNot AvailableInsulin Sensitivity / Obstructive Sleep Apnea (OSA)1
Not AvailableUnknown StatusBasic ScienceBMI >30 kg/m2 / Cardiovascular Disease (CVD) / Type 2 Diabetes Mellitus1
Not AvailableUnknown StatusBasic SciencePolycystic Ovaries Syndrome1
Not AvailableUnknown StatusTreatmentMetabolic Parameters and Liver Histology1
Not AvailableWithdrawnTreatmentAtopic Dermatitis (AD)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Advanced Pharmaceutical Services Inc.
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Atlantic Biologicals Corporation
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • DispenseXpress Inc.
  • Diversified Healthcare Services Inc.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmacy Service Center
  • Physician Partners Ltd.
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Quality Care
  • Rebel Distributors Corp.
  • Resource Optimization and Innovation LLC
  • Southwood Pharmaceuticals
  • Takeda Pharmaceutical Co. Ltd.
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
Tablet, film coated, extended releaseOral
TabletOcclusive dressing technique15 mg/1
TabletOcclusive dressing technique30 mg/1
TabletOral15 mg/1
TabletOral30 mg/1
TabletOral45 mg/1
Tablet, film coatedOral
TabletOral
TabletOral15 mg
TabletOral30 mg
TabletOral45 mg
Prices
Unit descriptionCostUnit
Actos 30 mg tablet12.48USD tablet
Actos 45 mg tablet11.22USD tablet
Actos 15 mg tablet6.3USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US4687777No1994-01-172011-01-17Us
CA2179584No2007-04-242016-06-20Canada
CA2531834No2006-12-052016-06-20Canada
US6150383No1996-06-192016-06-19Us
US6211205No1996-06-192016-06-19Us
US6303640No1996-08-092016-08-09Us
US6329404No1996-06-192016-06-19Us
US8071130No2008-06-082028-06-08Us
US7538125No1996-06-192016-06-19Us
US7700128No2007-01-302027-01-30Us
US5965584No1996-06-192016-06-19Us
US6166042No1996-06-192016-06-19Us
US6166043No1996-06-192016-06-19Us
US6172090No1996-06-192016-06-19Us
US6790459No2001-03-172021-03-17Us
US7919116No1998-03-202018-03-20Us
US8475841No1998-03-202018-03-20Us
US6099859No1998-03-202018-03-20Us
US6866866No2001-03-172021-03-17Us
US7785627No2006-07-312026-07-31Us
US7959946No2006-07-312026-07-31Us
US8470368No2003-09-192023-09-19Us
US8668931No2003-09-192023-09-19Us
US9060941No2003-09-192023-09-19Us
US6495162No1998-03-202018-03-20Us
US6150384No1996-06-192016-06-19Us
US6271243No1996-06-192016-06-19Us
US9101660No2007-01-222027-01-22Us
US6303661No1997-04-242017-04-24Us
US6890898No1999-02-022019-02-02Us
US7078381No1999-02-022019-02-02Us
US7459428No1999-02-022019-02-02Us
US7807689No2008-06-272028-06-27Us
US8173663No2005-03-152025-03-15Us
US8288539No2005-03-152025-03-15Us
US8637079No2009-06-042029-06-04Us
US9320714No2009-02-032029-02-03Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)183-184 °CNot Available
water solubilitymg/mLNot Available
logP2.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00442 mg/mLALOGPS
logP3.17ALOGPS
logP3.33ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)6.66ChemAxon
pKa (Strongest Basic)5.6ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area68.29 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity97.39 m3·mol-1ChemAxon
Polarizability37.91 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9952
Blood Brain Barrier+0.8753
Caco-2 permeable-0.5659
P-glycoprotein substrateNon-substrate0.6358
P-glycoprotein inhibitor INon-inhibitor0.5708
P-glycoprotein inhibitor IINon-inhibitor0.9673
Renal organic cation transporterNon-inhibitor0.6018
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5267
CYP450 1A2 substrateInhibitor0.8384
CYP450 2C9 inhibitorInhibitor0.6353
CYP450 2D6 inhibitorNon-inhibitor0.8085
CYP450 2C19 inhibitorInhibitor0.6967
CYP450 3A4 inhibitorNon-inhibitor0.6035
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8864
Ames testNon AMES toxic0.7303
CarcinogenicityNon-carcinogens0.9171
BiodegradationNot ready biodegradable0.7884
Rat acute toxicity2.0115 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9341
hERG inhibition (predictor II)Non-inhibitor0.8498
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0009000000-070cf69939743719671d
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0bt9-0209000000-d9d34be41f49a9ffbdef
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0900000000-ef25b6f93ae4fcee23c3
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0udi-0900000000-3011f00e839bfc06d89d
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0gba-0900000000-b0488e0d155d1587bbb5
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-014j-0900000000-b32570ad6af58a4a6c72
LC-MS/MS Spectrum - LC-ESI-QFT , negativeLC-MS/MSsplash10-0a4i-0009000000-c67370f6cb2ad36cab3e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a59-0908000000-aab2ee9addb1334a7064
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0009000000-fd4bc4d9d4bb45e91295
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-0409000000-115c6889c4e9205b3028
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-a2e878da4d2f6a4bb717
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-001i-0900000000-031fa259cd3b26217dad
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-00lr-0900000000-e2cd3c294a2e53e1a17e
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0159-1900000000-aacbd8dce006b5ef5938
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-1619000000-4b248e31af7f50e87108
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-053r-0906000000-a73152b364036b45dfeb

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Thiazolidinediones / Alkyl aryl ethers / Pyridines and derivatives / Heteroaromatic compounds / Dicarboximides / Thiocarbamic acid derivatives / Organic carbonic acids and derivatives / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
Phenoxy compound / Phenol ether / Alkyl aryl ether / Thiazolidinedione / Monocyclic benzene moiety / Pyridine / Dicarboximide / Heteroaromatic compound / Thiazolidine / Carbonic acid derivative
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, pyridines, thiazolidenediones (CHEBI:8228)

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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Sugii S, Olson P, Sears DD, Saberi M, Atkins AR, Barish GD, Hong SH, Castro GL, Yin YQ, Nelson MC, Hsiao G, Greaves DR, Downes M, Yu RT, Olefsky JM, Evans RM: PPARgamma activation in adipocytes is sufficient for systemic insulin sensitization. Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22504-9. doi: 10.1073/pnas.0912487106. Epub 2009 Dec 16. [PubMed:20018750]
  3. Miyazaki Y, Mahankali A, Wajcberg E, Bajaj M, Mandarino LJ, DeFronzo RA: Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2004 Sep;89(9):4312-9. [PubMed:15356026]
  4. Lehmann JM, Moore LB, Smith-Oliver TA, Wilkison WO, Willson TM, Kliewer SA: An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem. 1995 Jun 2;270(22):12953-6. [PubMed:7768881]
  5. Spiegelman BM: PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998 Apr;47(4):507-14. [PubMed:9568680]
  6. Willson TM, Cobb JE, Cowan DJ, Wiethe RW, Correa ID, Prakash SR, Beck KD, Moore LB, Kliewer SA, Lehmann JM: The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem. 1996 Feb 2;39(3):665-8. [PubMed:8576907]
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]
  2. Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [PubMed:23843199]
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
Primary amine oxidase activity
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOB
Uniprot ID
P27338
Uniprot Name
Amine oxidase [flavin-containing] B
Molecular Weight
58762.475 Da
References
  1. Binda C, Aldeco M, Geldenhuys WJ, Tortorici M, Mattevi A, Edmondson DE: Molecular Insights into Human Monoamine Oxidase B Inhibition by the Glitazone Anti-Diabetes Drugs. ACS Med Chem Lett. 2011 Oct 15;3(1):39-42. [PubMed:22282722]

Enzymes

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. Muschler E, Lal J, Jetter A, Rattay A, Zanger U, Zadoyan G, Fuhr U, Kirchheiner J: The role of human CYP2C8 and CYP2C9 variants in pioglitazone metabolism in vitro. Basic Clin Pharmacol Toxicol. 2009 Dec;105(6):374-9. doi: 10.1111/j.1742-7843.2009.00457.x. Epub 2009 Jul 15. [PubMed:19614891]
  2. Jaakkola T, Laitila J, Neuvonen PJ, Backman JT: Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol. 2006 Jul;99(1):44-51. [PubMed:16867170]
  3. Sahi J, Black CB, Hamilton GA, Zheng X, Jolley S, Rose KA, Gilbert D, LeCluyse EL, Sinz MW: Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab Dispos. 2003 Apr;31(4):439-46. [PubMed:12642470]
  4. 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]
  5. 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
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. Jaakkola T, Laitila J, Neuvonen PJ, Backman JT: Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors. Basic Clin Pharmacol Toxicol. 2006 Jul;99(1):44-51. [PubMed:16867170]
  2. Sahi J, Black CB, Hamilton GA, Zheng X, Jolley S, Rose KA, Gilbert D, LeCluyse EL, Sinz MW: Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition. Drug Metab Dispos. 2003 Apr;31(4):439-46. [PubMed:12642470]
  3. Nowak SN, Edwards DJ, Clarke A, Anderson GD, Jaber LA: Pioglitazone: effect on CYP3A4 activity. J Clin Pharmacol. 2002 Dec;42(12):1299-302. [PubMed:12463723]
  4. 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]
  5. 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
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 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
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]
  2. Papoushek C: The "glitazones": rosiglitazone and pioglitazone. J Obstet Gynaecol Can. 2003 Oct;25(10):853-7. [PubMed:14532954]

Transporters

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 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
Gene Name
SLCO1B3
Uniprot ID
Q9NPD5
Uniprot Name
Solute carrier organic anion transporter family member 1B3
Molecular Weight
77402.175 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]
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 November 14, 2018 12:50