PIOGLITAZONE

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

Structure Search

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)

HIDE SMILES / InChI

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	( + / - )

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021073s048lbl.pdf
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

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Peroxisome proliferator-activated receptor gamma 118 Target ID: CHEMBL235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26595749	Partial Agonist 297		200.0 nM [EC50]
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11831892	Partial Agonist 297		6680.0 nM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Type 2 diabetes mellitus 262 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021073s048lbl.pdf	Primary	Approved 8583	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
X-linked adrenoleukodystrophy 8 Sources: http://reference.medscape.com/drug/actos-pioglitazone-342726	Primary	Approved 8583	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
Friedreich ataxia 12 Sources: https://clinicaltrials.gov/ct2/show/NCT00811681	Primary	Phase III 665	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

C_max

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

T_1/2

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
Suppression of NF-kappaB and GSK-3beta is involved in colon cancer cell growth inhibition by the PPAR agonist troglitazone.	2010-10-06	20540935
Differential modulatory effects of rosiglitazone and pioglitazone on white adipose tissue in db/db mice.	2010-09-25	20723549
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	20450929
Rosiglitazone attenuates development of polycystic kidney disease and prolongs survival in Han:SPRD rats.	2010-07-09	20507283
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	20427483
Different effects of pioglitazone and rosiglitazone on lipid metabolism in mouse cultured liver explants.	2010-05	20503262
The role of adiponectin in the pathogenesis and treatment of non-alcoholic fatty liver disease.	2010-05	20415685
Rational design of a pirinixic acid derivative that acts as subtype-selective PPARgamma modulator.	2010-04-15	20307981
Computer-aided discovery, validation, and mechanistic characterization of novel neolignan activators of peroxisome proliferator-activated receptor gamma.	2010-04	20064974
Effects of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on the urine and urothelium of the rat.	2010-02	19858066
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	19959591
Peroxisome proliferator-activated receptor gamma agonist rosiglitazone increases expression of very low density lipoprotein receptor gene in adipocytes.	2009-10-30	19706614
Emerging treatments in cystic fibrosis.	2009-10-01	19747007
On the mechanism for PPAR agonists to enhance ABCA1 gene expression.	2009-08	19201410
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	19208898
Effects of benzbromarone and allopurinol on adiponectin in vivo and in vitro.	2009-04	19048458
Type 2 deiodinase expression is induced by peroxisomal proliferator-activated receptor-gamma agonists in skeletal myocytes.	2009-04	19036883
Differential effects of in vivo PPAR alpha and gamma activation on fatty acid transport proteins expression and lipid content in rat liver.	2009-03	19439812
Retinol saturase promotes adipogenesis and is downregulated in obesity.	2009-01-27	19139408
Distinct functions of vascular endothelial and smooth muscle PPARgamma in regulation of blood pressure and vascular tone.	2009-01	19075043
Chronic, in vivo, PPARalpha activation prevents lipid overload in rat liver induced by high fat feeding.	2009	19403437
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	18513333
Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho/Rho-kinase, and PPARs in cardiomyocytes.	2008-09	18660453
Treating Hispanic patients for type 2 diabetes mellitus: special considerations.	2008-05	18519840
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	18303122
Inhibition of advanced glycation end products: an implicit goal in clinical medicine for the treatment of diabetic nephropathy?	2008-04	18448808
Telmisartan inhibits CD4-positive lymphocyte migration independent of the angiotensin type 1 receptor via peroxisome proliferator-activated receptor-gamma.	2008-02	18158351
NR4A orphan nuclear receptors modulate insulin action and the glucose transport system: potential role in insulin resistance.	2007-10-26	17785466
Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials.	2007-09-12	17848652
MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone.	2007-09-04	17766440
[Effects of peroxisome proliferators activated receptors on caveolin-1 expression in foam cells].	2007-07	17961437
The PPARgamma agonist pioglitazone inhibits early neoplastic occurrence in the rat liver.	2007-07	17582756
Inhibitory effect of PPAR on the expression of EMMPRIN in macrophages and foam cells.	2007-05-02	16860414
Ligands of peroxisome proliferator-activated receptor inhibit homocysteine-induced DNA methylation of inducible nitric oxide synthase gene.	2007-05	17492134
Peroxisome proliferator-activated receptor gamma activation relieves expression of behavioral sensitization to methamphetamine in mice.	2007-05	17019405
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	17394460
Pioglitazone inhibits androgen production in NCI-H295R cells by regulating gene expression of CYP17 and HSD3B2.	2007-03	17138841
Troglitazone and pioglitazone interactions via PPAR-gamma-independent and -dependent pathways in regulating physiological responses in renal tubule-derived cell lines.	2007-03	17065204
Resveratrol inhibits macrophage expression of EMMPRIN by activating PPARgamma.	2007-02	17055343
Effect of pioglitazone treatment on behavioral symptoms in autistic children.	2007-01-05	17207275
Peroxisome proliferated-activated receptor gamma ligand, Pioglitazone, does not prevent hepatic fibrosis in mice.	2007-01	17143554
Activating effect of benzbromarone, a uricosuric drug, on peroxisome proliferator-activated receptors.	2007	18274627
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	17084873
Rosiglitazone inhibits mouse liver regeneration.	2006-12	17077279
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	16979161
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	17015710
Acetaldehyde inhibits PPARgamma via H2O2-mediated c-Abl activation in human hepatic stellate cells.	2006-10	17030193
[Effects of pioglitazone on MKP-1 and TSP-1 expression in early stages of diabetic retinopathy induced by streptozotocin].	2006-09	17063547
Augmentation of myocardial production of 15-epi-lipoxin-a4 by pioglitazone and atorvastatin in the rat.	2006-08-29	16908763
[Resveratrol inhibits expression of EMMPRIN from macrophages].	2006-07	17007354

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Wed Apr 02 07:40:05 GMT 2025` Edited by `admin` on `Wed Apr 02 07:40:05 GMT 2025`
Record UNII	X4OV71U42S
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PIOGLITAZONE

Official Name

English

GLUSTIN

Preferred Name

English

5-(4-(2-(5-ETHYLPYRIDIN-2-YL)ETHOXY)BENZYL)THIAZOLIDINE-2,4-DIONE

Systematic Name

English

PIOGLITAZONE [MI]

Common Name

English

pioglitazone [INN]

Common Name

English

ZACTOS

Brand Name

English

5-((4-(2-(5-ETHYL-2-PYRIDINYL)ETHOXY)PHENYL)METHYL)-2,4-THIAZOLIDINEDIONE

Systematic Name

English

AD-4833

Code

English

PIOGLITAZONE [EMA EPAR]

Common Name

English

PIOGLITAZONE [VANDF]

Common Name

English

(RS)-5-(4-(2-(5-ETHYLPYRIDIN-2-YL)ETHOXY)BENZYL)THIAZOLIDINE-2,4-DIONE

Systematic Name

English

2,4-THIAZOLIDINEDIONE, 5-((4-(2-(5-ETHYL-2-PYRIDINYL)ETHOXY)PHENYL)METHYL)-, (±)-

Systematic Name

English

PIOGLITAZONE [HSDB]

Common Name

English

2,4-THIAZOLIDINEDIONE, 5-((4-(2-(5-ETHYL-2-PYRIDINYL)ETHOXY)PHENYL)METHYL)-

Systematic Name

English

PIOGLITAZONE [IARC]

Common Name

English

Pioglitazone [WHO-DD]

Common Name

English

U-72107

Code

English

(±)-5-(P-(2-(5-ETHYL-2-PYRIDYL)ETHOXY)BENZYL)-2,4-THIAZOLIDINEDIONE

Common Name

English

5-(4-(2-(5-ETHYL-2-PYRIDYL)ETHOXY)BENZYL)THIAZOLIDINE-2,4-DIONE

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000170118