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
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	11687581
Pioglitazone-associated fulminant hepatic failure.	2002 Feb	11866308
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.	2002 Jan 11	11779144
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size.	2002 Jul	12087064
Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro.	2002 Jun	12055599
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	12044893
Peroxisome proliferator-activated receptor gamma ligands suppress liver carcinogenesis induced by diethylnitrosamine in rats.	2004 Dec 1	15526359
A yeast two-hybrid technology-based system for the discovery of PPARgamma agonist and antagonist.	2004 Dec 15	15556564
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	15150131
Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation.	2004 Oct 22	15381068
Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice.	2005 Jun	15817521
Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone.	2005 May	15900286
Regulatory effects of synthetic liver X receptor- and peroxisome-proliferator activated receptor agonists on sterol transport pathways in polarized cerebrovascular endothelial cells.	2006	16530456
Augmentation of myocardial production of 15-epi-lipoxin-a4 by pioglitazone and atorvastatin in the rat.	2006 Aug 29	16908763
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	17084873
[Resveratrol inhibits expression of EMMPRIN from macrophages].	2006 Jul	17007354
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	16611854
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	16597547
Peroxisome proliferator-activated receptor-gamma agonist is protective in podocyte injury-associated sclerosis.	2006 May	16598202
Use of immortalized human hepatocytes to predict the magnitude of clinical drug-drug interactions caused by CYP3A4 induction.	2006 Oct	16837568
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	17394460
Resveratrol inhibits macrophage expression of EMMPRIN by activating PPARgamma.	2007 Feb	17055343
The PPARgamma agonist pioglitazone inhibits early neoplastic occurrence in the rat liver.	2007 Jul	17582756
Pioglitazone inhibits androgen production in NCI-H295R cells by regulating gene expression of CYP17 and HSD3B2.	2007 Mar	17138841
Inhibitory effect of PPAR on the expression of EMMPRIN in macrophages and foam cells.	2007 May 2	16860414
Pioglitazone and risk of cardiovascular events in patients with type 2 diabetes mellitus: a meta-analysis of randomized trials.	2007 Sep 12	17848652
MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone.	2007 Sep 4	17766440
Telmisartan inhibits CD4-positive lymphocyte migration independent of the angiotensin type 1 receptor via peroxisome proliferator-activated receptor-gamma.	2008 Feb	18158351
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	18513333
Rational design of a pirinixic acid derivative that acts as subtype-selective PPARgamma modulator.	2010 Apr 15	20307981
Effects of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on the urine and urothelium of the rat.	2010 Feb	19858066
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	20427483

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