U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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 of PIOGLITAZONE

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
MOL RATIO 1 MOL RATIO (average)
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description

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 TargetPharmacologyConditionPotency
200.0 nM [EC50]
6680.0 nM [EC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ACTOS
Primary
ACTOS
Primary
ACTOS

Cmax

ValueDoseCo-administeredAnalytePopulation
890 ng/mL
45 mg 1 times / day steady-state, oral
PIOGLITAZONE plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
8662 ng × h/mL
45 mg 1 times / day steady-state, oral
PIOGLITAZONE plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
12.6 h
45 mg 1 times / day steady-state, oral
PIOGLITAZONE plasma
Homo sapiens

Doses

AEs

PubMed

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
Record UNII
X4OV71U42S
Record Status Validated (UNII)
Record Version