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Details

Stereochemistry RACEMIC
Molecular Formula C19H19N2O3S.Na
Molecular Weight 378.421
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PIOGLITAZONE SODIUM

SMILES

[Na+].CCC1=CC=C(CCOC2=CC=C(CC3SC(=O)[N-]C3=O)C=C2)N=C1

InChI

InChIKey=SQHZCSKYFSLBLG-UHFFFAOYSA-M
InChI=1S/C19H20N2O3S.Na/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);/q;+1/p-1

HIDE SMILES / InChI

Description
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.

Originator

Curator's Comment: # Takeda Chemical Industries, Ltd

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ACTOS

Approved Use

Pioglitazone 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 Date

1999
Primary
ACTOS

Approved Use

Pioglitazone 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 Date

1999
Primary
ACTOS

Approved Use

Pioglitazone 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 Date

1999
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
890 ng/mL
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

AUC

ValueDoseCo-administeredAnalytePopulation
8662 ng × h/mL
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

T1/2

ValueDoseCo-administeredAnalytePopulation
12.6 h
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

PubMed

TitleDatePubMed
Suppression of NF-kappaB and GSK-3beta is involved in colon cancer cell growth inhibition by the PPAR agonist troglitazone.
2010-10-06
Differential modulatory effects of rosiglitazone and pioglitazone on white adipose tissue in db/db mice.
2010-09-25
Pioglitazone ameliorates behavioral, biochemical and cellular alterations in quinolinic acid induced neurotoxicity: possible role of peroxisome proliferator activated receptor-Upsilon (PPARUpsilon) in Huntington's disease.
2010-08
Rosiglitazone attenuates development of polycystic kidney disease and prolongs survival in Han:SPRD rats.
2010-07-09
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.
2010-06
Different effects of pioglitazone and rosiglitazone on lipid metabolism in mouse cultured liver explants.
2010-05
The role of adiponectin in the pathogenesis and treatment of non-alcoholic fatty liver disease.
2010-05
Rational design of a pirinixic acid derivative that acts as subtype-selective PPARgamma modulator.
2010-04-15
Computer-aided discovery, validation, and mechanistic characterization of novel neolignan activators of peroxisome proliferator-activated receptor gamma.
2010-04
Effects of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on the urine and urothelium of the rat.
2010-02
Risk of cardiovascular disease and all cause mortality among patients with type 2 diabetes prescribed oral antidiabetes drugs: retrospective cohort study using UK general practice research database.
2009-12-03
Peroxisome proliferator-activated receptor gamma agonist rosiglitazone increases expression of very low density lipoprotein receptor gene in adipocytes.
2009-10-30
Emerging treatments in cystic fibrosis.
2009-10-01
On the mechanism for PPAR agonists to enhance ABCA1 gene expression.
2009-08
Chronic administration of voglibose, an alpha-glucosidase inhibitor, increases active glucagon-like peptide-1 levels by increasing its secretion and decreasing dipeptidyl peptidase-4 activity in ob/ob mice.
2009-05
Effects of benzbromarone and allopurinol on adiponectin in vivo and in vitro.
2009-04
Type 2 deiodinase expression is induced by peroxisomal proliferator-activated receptor-gamma agonists in skeletal myocytes.
2009-04
Differential effects of in vivo PPAR alpha and gamma activation on fatty acid transport proteins expression and lipid content in rat liver.
2009-03
Retinol saturase promotes adipogenesis and is downregulated in obesity.
2009-01-27
Distinct functions of vascular endothelial and smooth muscle PPARgamma in regulation of blood pressure and vascular tone.
2009-01
Chronic, in vivo, PPARalpha activation prevents lipid overload in rat liver induced by high fat feeding.
2009
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.
2008-10
Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho/Rho-kinase, and PPARs in cardiomyocytes.
2008-09
Treating Hispanic patients for type 2 diabetes mellitus: special considerations.
2008-05
JNK- and IkappaB-dependent pathways regulate MCP-1 but not adiponectin release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro.
2008-05
Inhibition of advanced glycation end products: an implicit goal in clinical medicine for the treatment of diabetic nephropathy?
2008-04
Telmisartan inhibits CD4-positive lymphocyte migration independent of the angiotensin type 1 receptor via peroxisome proliferator-activated receptor-gamma.
2008-02
NR4A orphan nuclear receptors modulate insulin action and the glucose transport system: potential role in insulin resistance.
2007-10-26
Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials.
2007-09-12
MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone.
2007-09-04
[Effects of peroxisome proliferators activated receptors on caveolin-1 expression in foam cells].
2007-07
The PPARgamma agonist pioglitazone inhibits early neoplastic occurrence in the rat liver.
2007-07
Inhibitory effect of PPAR on the expression of EMMPRIN in macrophages and foam cells.
2007-05-02
Ligands of peroxisome proliferator-activated receptor inhibit homocysteine-induced DNA methylation of inducible nitric oxide synthase gene.
2007-05
Peroxisome proliferator-activated receptor gamma activation relieves expression of behavioral sensitization to methamphetamine in mice.
2007-05
Peroxisome proliferator-activated receptor-gamma agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents.
2007-04
Pioglitazone inhibits androgen production in NCI-H295R cells by regulating gene expression of CYP17 and HSD3B2.
2007-03
Troglitazone and pioglitazone interactions via PPAR-gamma-independent and -dependent pathways in regulating physiological responses in renal tubule-derived cell lines.
2007-03
Resveratrol inhibits macrophage expression of EMMPRIN by activating PPARgamma.
2007-02
Effect of pioglitazone treatment on behavioral symptoms in autistic children.
2007-01-05
Peroxisome proliferated-activated receptor gamma ligand, Pioglitazone, does not prevent hepatic fibrosis in mice.
2007-01
Activating effect of benzbromarone, a uricosuric drug, on peroxisome proliferator-activated receptors.
2007
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.
2006-12-15
Rosiglitazone inhibits mouse liver regeneration.
2006-12
The direct antioxidative and anti-inflammatory effects of peroxisome proliferator-activated receptors ligands are associated with the inhibition of angiotensin converting enzyme expression in streptozotocin-induced diabetic rat aorta.
2006-11-07
Modulation of airway remodeling and airway inflammation by peroxisome proliferator-activated receptor gamma in a murine model of toluene diisocyanate-induced asthma.
2006-10-15
Acetaldehyde inhibits PPARgamma via H2O2-mediated c-Abl activation in human hepatic stellate cells.
2006-10
[Effects of pioglitazone on MKP-1 and TSP-1 expression in early stages of diabetic retinopathy induced by streptozotocin].
2006-09
Augmentation of myocardial production of 15-epi-lipoxin-a4 by pioglitazone and atorvastatin in the rat.
2006-08-29
[Resveratrol inhibits expression of EMMPRIN from macrophages].
2006-07
Patents

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
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
Name Type Language
PIOGLITAZONE SODIUM
Common Name English
2,4-THIAZOLIDINEDIONE, 5-((4-(2-(5-ETHYL-2-PYRIDINYL)ETHOXY)PHENYL)METHYL)-, SODIUM SALT
Preferred Name English
2,4-THIAZOLIDINEDIONE, 5-((4-(2-(5-ETHYL-2-PYRIDINYL)ETHOXY)PHENYL)METHYL)-, SODIUM SALT (1:1)
Common Name English
Code System Code Type Description
EPA CompTox
DTXSID70694834
Created by admin on Mon Mar 31 23:21:30 GMT 2025 , Edited by admin on Mon Mar 31 23:21:30 GMT 2025
PRIMARY
CAS
105390-47-4
Created by admin on Mon Mar 31 23:21:30 GMT 2025 , Edited by admin on Mon Mar 31 23:21:30 GMT 2025
PRIMARY
PUBCHEM
25210761
Created by admin on Mon Mar 31 23:21:30 GMT 2025 , Edited by admin on Mon Mar 31 23:21:30 GMT 2025
PRIMARY
FDA UNII
8X7M0J4NMU
Created by admin on Mon Mar 31 23:21:30 GMT 2025 , Edited by admin on Mon Mar 31 23:21:30 GMT 2025
PRIMARY