Details
Stereochemistry | RACEMIC |
Molecular Formula | C19H20N2O3S |
Molecular Weight | 356.439 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCC1=CC=C(CCOC2=CC=C(CC3SC(=O)NC3=O)C=C2)N=C1
InChI
InChIKey=HYAFETHFCAUJAY-UHFFFAOYSA-N
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)
Molecular Formula | C19H20N2O3S |
Molecular Weight | 356.439 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
DescriptionCurator's Comment: description was created based on several sources, including
http://reference.medscape.com/drug/actos-pioglitazone-342726 | https://www.drugbank.ca/drugs/DB01132 | https://www.drugs.com/cdi/pioglitazone.html | https://www.ncbi.nlm.nih.gov/pubmed/25760794
Curator's Comment: description was created based on several sources, including
http://reference.medscape.com/drug/actos-pioglitazone-342726 | https://www.drugbank.ca/drugs/DB01132 | https://www.drugs.com/cdi/pioglitazone.html | https://www.ncbi.nlm.nih.gov/pubmed/25760794
Pioglitazone (brand name Actos) is a prescription drug of the thiazolidinedione class with hypoglycemic action used in the treatment of type 2 diabetes. Pioglitazone selectively stimulates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and to a lesser extent PPAR-α. It modulates the transcription of the genes involved in the control of glucose and lipid metabolism in the muscle, adipose tissue, and the liver. As a result, pioglitazone reduces insulin resistance in the liver and peripheral tissues, decreases gluconeogenesis in the liver, and reduces the quantity of glucose and glycated hemoglobin in the bloodstream. Pioglitazone is used to lower blood glucose levels in the treatment of diabetes mellitus type 2 (T2DM) either alone or in combination with a sulfonylurea, metformin, or insulin. Pioglitazone cannot be used in patients with a known hypersensitivity to pioglitazone, other thiazolidinediones or any of components of its pharmaceutical forms. It is ineffective and possibly harmful to diabetes mellitus type 1 and diabetic ketoacidosis. Pioglitazone can cause fluid retention and peripheral edema. As a result, it may precipitate congestive heart failure (which worsens with fluid overload in those at risk). It may cause anemia. Mild weight gain is common due to increase in subcutaneous adipose tissue. In studies, patients on pioglitazone had an increased proportion of upper respiratory tract infection, sinusitis, headache, myalgia and tooth problems.
CNS Activity
Originator
Sources: https://www.google.ch/patents/EP0193256
Curator's Comment: # Takeda Chemical Industries, Ltd
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26595749 |
200.0 nM [EC50] | ||
Target ID: CHEMBL239 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11831892 |
6680.0 nM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | ACTOS Approved UsePioglitazone tablets are a thiazolidinedione and an agonist for peroxisome proliferator-activated receptor (PPAR) gamma indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings. (1.1, 14) Important Limitation of Use: •Not for treatment of type 1 diabetes or diabetic ketoacidosis. (1.2) 1.1 Monotherapy and Combination Therapy Pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings [see Clinical Studies (14) Launch Date1999 |
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Primary | ACTOS Approved UsePioglitazone tablets are a thiazolidinedione and an agonist for peroxisome proliferator-activated receptor (PPAR) gamma indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings. (1.1, 14) Important Limitation of Use: •Not for treatment of type 1 diabetes or diabetic ketoacidosis. (1.2) 1.1 Monotherapy and Combination Therapy Pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings [see Clinical Studies (14) Launch Date1999 |
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Primary | ACTOS Approved UsePioglitazone tablets are a thiazolidinedione and an agonist for peroxisome proliferator-activated receptor (PPAR) gamma indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings. (1.1, 14) Important Limitation of Use: •Not for treatment of type 1 diabetes or diabetic ketoacidosis. (1.2) 1.1 Monotherapy and Combination Therapy Pioglitazone tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings [see Clinical Studies (14) Launch Date1999 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
890 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16172178 |
45 mg 1 times / day steady-state, oral dose: 45 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
PIOGLITAZONE plasma | Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
8662 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16172178 |
45 mg 1 times / day steady-state, oral dose: 45 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
PIOGLITAZONE plasma | Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
12.6 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16172178 |
45 mg 1 times / day steady-state, oral dose: 45 mg route of administration: Oral experiment type: STEADY-STATE co-administered: |
PIOGLITAZONE plasma | Homo sapiens population: UNHEALTHY age: ADOLESCENT sex: FEMALE / MALE food status: FED |
PubMed
Title | Date | PubMed |
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15-Deoxy-delta 12,14-prostaglandin J2 and thiazolidinediones activate the MEK/ERK pathway through phosphatidylinositol 3-kinase in vascular smooth muscle cells. | 2001 Dec 28 |
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Pioglitazone-associated fulminant hepatic failure. | 2002 Feb |
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Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB. | 2002 Jan 11 |
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Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size. | 2002 Jul |
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Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro. | 2002 Jun |
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PPAR gamma ligands, troglitazone and pioglitazone, up-regulate expression of HMG-CoA synthase and HMG-CoA reductase gene in THP-1 macrophages. | 2002 Jun 5 |
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Peroxisome proliferator-activated receptor gamma ligands suppress liver carcinogenesis induced by diethylnitrosamine in rats. | 2004 Dec 1 |
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A yeast two-hybrid technology-based system for the discovery of PPARgamma agonist and antagonist. | 2004 Dec 15 |
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Transactivation of the PPAR-responsive enhancer module in chemopreventive glutathione S-transferase gene by the peroxisome proliferator-activated receptor-gamma and retinoid X receptor heterodimer. | 2004 May 15 |
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Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation. | 2004 Oct 22 |
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Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice. | 2005 Jun |
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Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. | 2005 May |
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Regulatory effects of synthetic liver X receptor- and peroxisome-proliferator activated receptor agonists on sterol transport pathways in polarized cerebrovascular endothelial cells. | 2006 |
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Augmentation of myocardial production of 15-epi-lipoxin-a4 by pioglitazone and atorvastatin in the rat. | 2006 Aug 29 |
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In vitro screening of 200 pesticides for agonistic activity via mouse peroxisome proliferator-activated receptor (PPAR)alpha and PPARgamma and quantitative analysis of in vivo induction pathway. | 2006 Dec 15 |
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[Resveratrol inhibits expression of EMMPRIN from macrophages]. | 2006 Jul |
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Peroxisome proliferator-activated receptor-gamma and retinoic acid X receptor alpha represses the TGFbeta1 gene via PTEN-mediated p70 ribosomal S6 kinase-1 inhibition: role for Zf9 dephosphorylation. | 2006 Jul |
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Gene expression analysis of troglitazone reveals its impact on multiple pathways in cell culture: a case for in vitro platforms combined with gene expression analysis for early (idiosyncratic) toxicity screening. | 2006 Mar-Apr |
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Peroxisome proliferator-activated receptor-gamma agonist is protective in podocyte injury-associated sclerosis. | 2006 May |
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Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction. | 2006 Oct |
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Peroxisome proliferator-activated receptor-gamma agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents. | 2007 Apr |
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Resveratrol inhibits macrophage expression of EMMPRIN by activating PPARgamma. | 2007 Feb |
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The PPARgamma agonist pioglitazone inhibits early neoplastic occurrence in the rat liver. | 2007 Jul |
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Pioglitazone inhibits androgen production in NCI-H295R cells by regulating gene expression of CYP17 and HSD3B2. | 2007 Mar |
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Inhibitory effect of PPAR on the expression of EMMPRIN in macrophages and foam cells. | 2007 May 2 |
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Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials. | 2007 Sep 12 |
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MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone. | 2007 Sep 4 |
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Telmisartan inhibits CD4-positive lymphocyte migration independent of the angiotensin type 1 receptor via peroxisome proliferator-activated receptor-gamma. | 2008 Feb |
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Bezafibrate prevents hepatic stellate cell activation and fibrogenesis in a murine steatohepatitis model, and suppresses fibrogenic response induced by transforming growth factor-beta1 in a cultured stellate cell line. | 2008 Oct |
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Rational design of a pirinixic acid derivative that acts as subtype-selective PPARgamma modulator. | 2010 Apr 15 |
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Effects of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on the urine and urothelium of the rat. | 2010 Feb |
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Troglitazone, a ligand of peroxisome proliferator-activated receptor-{gamma}, stabilizes NUCB2 (Nesfatin) mRNA by activating the ERK1/2 pathway: isolation and characterization of the human NUCB2 gene. | 2010 Jun |
Sample Use Guides
Initiate ACTOS (Pioglitazone) at 15 mg or 30 mg once daily. Limit initial dose to 15 mg once daily in patients with NYHA Class I or II heart failure.
If there is inadequate glycemic control, the dose can be increased in 15 mg increments up to a maximum of 45 mg once daily.
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27703271
For the cell counting assay, Human aortic smooth muscle cells (HASMCs) were seeded at 3× 10^3 cells on to a 96-well dish; 24 hours after the plating, the cells were serum-starved to render them quiescent by replacing the medium with DMEM containing 0.2% FBS. The quiescent SMCs were then preincubated with globular adiponectin (1μg/mL or 3μg/mL) or pioglitazone (1μM or 10μM) for 30min. PDGF-BB (10ng/mL) was added to stimulate the cells for 24hours. These cells were incubated with 10 μl of CCK (cell counting kit)-8 (DOJINDO) or WST-1 (Roche) solution for 2hours before conducting the measurements. We measured the absorbance at 450nm using a microplate reader. 10 μl of BrdU (Roche) solution was added these cells simultaneously with PDGF-BB. BrdU incorporation was measured by chemiluminescent assay
Substance Class |
Chemical
Created
by
admin
on
Edited
Wed Apr 02 07:40:05 GMT 2025
by
admin
on
Wed Apr 02 07:40:05 GMT 2025
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Record UNII |
X4OV71U42S
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Record Status |
Validated (UNII)
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Record Version |
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N0000180186
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EU/3/14/1245
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C98241
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N0000170118
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A10BG03
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N0000175596
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198077-89-3
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Pioglitazone
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DB01132
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C060836
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TRANSPORTER -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT | |||
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TRANSPORTER -> INHIBITOR |
IC50
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TARGET -> AGONIST | |||
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METABOLITE INACTIVE -> PARENT | |||
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METABOLITE INACTIVE -> PARENT | |||
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METABOLITE ACTIVE -> PARENT | |||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Biological Half-life | PHARMACOKINETIC |
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