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Details

Stereochemistry RACEMIC
Molecular Formula C18H19N3O3S.C4H4O4
Molecular Weight 473.499
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of ROSIGLITAZONE FUMARATE

SMILES

OC(=O)\C=C\C(O)=O.CN(CCOC1=CC=C(CC2SC(=O)NC2=O)C=C1)C3=CC=CC=N3

InChI

InChIKey=SUFUKZSWUHZXAV-WLHGVMLRSA-N
InChI=1S/C18H19N3O3S.C4H4O4/c1-21(16-4-2-3-9-19-16)10-11-24-14-7-5-13(6-8-14)12-15-17(22)20-18(23)25-15;5-3(6)1-2-4(7)8/h2-9,15H,10-12H2,1H3,(H,20,22,23);1-2H,(H,5,6)(H,7,8)/b;2-1+

HIDE SMILES / InChI

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Molecular Formula C18H19N3O3S
Molecular Weight 357.427
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Description
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/mtm/rosiglitazone.html http://www.rxlist.com/avandia-drug.htm http://www.wikidoc.org/index.php/Rosiglitazone

Rosiglitazone acts as a highly selective and potent agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. It is FDA approved for the treatment of as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Inhibitors of CYP2C8 (e.g., gemfibrozil) may increase rosiglitazone levels; inducers of CYP2C8 (e.g., rifampin) may decrease rosiglitazone levels. Common adverse reactions include edema, weight gain, and headache.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AVANDIA

Approved Use

After consultation with a healthcare professional who has considered and advised the patient of the risks and benefits of rosiglitazone, AVANDAMET® is indicated as an adjunct to diet and exercise to improve glycemic control when treatment with both rosiglitazone and metformin is appropriate in adults with type 2 diabetes mellitus who either are: already taking rosiglitazone, or not already taking rosiglitazone and unable to achieve glycemic control on other diabetes medications and, in consultation with their healthcare provider, have decided not to take pioglitazone (ACTOS®) or pioglitazone-containing products (ACTOPLUS MET®, ACTOPLUS MET XR®, DUETACT®) for medical reasons. Other Important Limitations of Use: Due to its mechanism of action, rosiglitazone is active only in the presence of endogenous insulin. Therefore, AVANDAMET should not be used in patients with type 1 diabetes. Coadministration of AVANDAMET with insulin is not recommended [see Warnings and Precautions (5.2, 5.3)

Launch Date

9.2759038E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
432 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FED
598 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2890 ng × h/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FED
2971 ng × h/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.59 h
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FED
3.37 h
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ROSIGLITAZONE plasma
Homo sapiens
population: UNKNOWN
age: ADULT
sex: UNKNOWN
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.105
unhealthy, 53.1
n = 32
Health Status: unhealthy
Condition: Nonalcoholic steatohepatitis
Age Group: 53.1
Sex: M+F
Population Size: 32
Sources: Page: p.105
DLT: Headache, Malaise...
Disc. AE: Pain in leg...
Dose limiting toxicities:
Headache (3.1%)
Malaise (3.1%)
Oedema legs (9.4%)
AEs leading to
discontinuation/dose reduction:
Pain in leg (3.1%)
Sources: Page: p.105
20 mg single, oral
Overdose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources: Page: p.73,74
unhealthy, 60
n = 1
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: 60
Sex: M
Population Size: 1
Sources: Page: p.73,74
Disc. AE: Macular edema...
AEs leading to
discontinuation/dose reduction:
Macular edema
Sources: Page: p.73,74
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Disc. AE: Congestive heart failure, Myocardial ischemia...
AEs leading to
discontinuation/dose reduction:
Congestive heart failure
Myocardial ischemia (2%)
Fluid retention
Edema
Weight gain
Anemia
Macular edema
Fracture bone
Sources: Page: p.1
AEs

AEs

AESignificanceDosePopulation
Headache 3.1%
DLT
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.105
unhealthy, 53.1
n = 32
Health Status: unhealthy
Condition: Nonalcoholic steatohepatitis
Age Group: 53.1
Sex: M+F
Population Size: 32
Sources: Page: p.105
Malaise 3.1%
DLT
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.105
unhealthy, 53.1
n = 32
Health Status: unhealthy
Condition: Nonalcoholic steatohepatitis
Age Group: 53.1
Sex: M+F
Population Size: 32
Sources: Page: p.105
Pain in leg 3.1%
Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.105
unhealthy, 53.1
n = 32
Health Status: unhealthy
Condition: Nonalcoholic steatohepatitis
Age Group: 53.1
Sex: M+F
Population Size: 32
Sources: Page: p.105
Oedema legs 9.4%
DLT
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.105
unhealthy, 53.1
n = 32
Health Status: unhealthy
Condition: Nonalcoholic steatohepatitis
Age Group: 53.1
Sex: M+F
Population Size: 32
Sources: Page: p.105
Macular edema Disc. AE
20 mg single, oral
Overdose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources: Page: p.73,74
unhealthy, 60
n = 1
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Age Group: 60
Sex: M
Population Size: 1
Sources: Page: p.73,74
Myocardial ischemia 2%
Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Anemia Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Congestive heart failure Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Edema Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Fluid retention Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Fracture bone Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Macular edema Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
Weight gain Disc. AE
8 mg 1 times / day multiple, oral
Recommended
Dose: 8 mg, 1 times / day
Route: oral
Route: multiple
Dose: 8 mg, 1 times / day
Sources: Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources: Page: p.1
PubMed

PubMed

TitleDatePubMed
Rosiglitazone (BRL49653), a PPARgamma-selective agonist, causes peroxisome proliferator-like liver effects in obese mice.
1999 Jul
v- and t-SNARE protein expression in models of insulin resistance: normalization of glycemia by rosiglitazone treatment corrects overexpression of cellubrevin, vesicle-associated membrane protein-2, and syntaxin 4 in skeletal muscle of Zucker diabetic fatty rats.
2000 Apr
Troglitazone inhibits mitogenic signaling by insulin in vascular smooth muscle cells.
2000 May
Synthesis and biological activity of L-tyrosine-based PPARgamma agonists with reduced molecular weight.
2001 Dec 17
Troglitazone and rosiglitazone induce apoptosis of vascular smooth muscle cells through an extracellular signal-regulated kinase-independent pathway.
2001 Feb
Insulin-sensitizing action of rosiglitazone is enhanced by preventing hyperphagia.
2001 Jun
Troglitazone treatment increases plasma vascular endothelial growth factor in diabetic patients and its mRNA in 3T3-L1 adipocytes.
2001 May
Unique ability of troglitazone to up-regulate peroxisome proliferator-activated receptor-gamma expression in hepatocytes.
2002 Jan
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size.
2002 Jul
Peroxisome proliferator-activated receptor agonists inhibit inflammatory edema and hyperalgesia.
2002 Jun
Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro.
2002 Jun
Accelerated hypertension due to rosiglitazone therapy.
2002 Nov-Dec
Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition.
2003 Apr
PPAR gamma-dependent anti-inflammatory action of rosiglitazone in human monocytes: suppression of TNF alpha secretion is not mediated by PTEN regulation.
2003 Apr 11
15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia.
2003 Apr 25
Expression of phosphoenolpyruvate carboxykinase gene in human adipose tissue: induction by rosiglitazone and genetic analyses of the adipocyte-specific region of the promoter in type 2 diabetes.
2003 Dec
Reduction in the evolution of murine type II collagen-induced arthritis by treatment with rosiglitazone, a ligand of the peroxisome proliferator-activated receptor gamma.
2003 Dec
Diminished production of nitric oxide synthase cofactor tetrahydrobiopterin by rosiglitazone in adipocytes.
2003 Feb 15
A human cell surface receptor activated by free fatty acids and thiazolidinedione drugs.
2003 Feb 7
Rosiglitazone reduces blood pressure and urinary albumin excretion in type 2 diabetes: G Bakris et al.
2003 Jan
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
Regulation of retinoic acid receptor beta expression by peroxisome proliferator-activated receptor gamma ligands in cancer cells.
2003 Jul 1
Induction of apoptosis by mono(2-ethylhexyl)phthalate (MEHP) in U937 cells.
2003 Oct 15
Cinnamic acid based thiazolidinediones inhibit human P450c17 and 3beta-hydroxysteroid dehydrogenase and improve insulin sensitivity independent of PPARgamma agonist activity.
2004 Apr
Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes.
2004 Aug
[Anti-hypertensive effect of rosiglitazone in non-diabetic essential hypertension].
2004 Dec
Effect of peroxisome proliferator-activated receptor gamma agonist, rosiglitazone, on dedifferentiated thyroid cancers.
2004 Dec
Bone is a target for the antidiabetic compound rosiglitazone.
2004 Jan
Rosiglitazone induction of Insig-1 in white adipose tissue reveals a novel interplay of peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding protein in the regulation of adipogenesis.
2004 Jun 4
Rosiglitazone facilitates angiogenic progenitor cell differentiation toward endothelial lineage: a new paradigm in glitazone pleiotropy.
2004 Mar 23
Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.
2004 May
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
Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone.
2004 Nov
Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro.
2004 Oct
The antidiabetic agent rosiglitazone upregulates SERCA2 and enhances TNF-alpha- and LPS-induced NF-kappaB-dependent transcription and TNF-alpha-induced IL-6 secretion in ventricular myocytes.
2005
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.
2005 Aug
Rosiglitazone, PPAR-gamma receptor ligand, decreases the viability of rat prolactin-secreting pituitary tumor cells in vitro.
2005 Feb
Enhanced insulin-stimulated glycogen synthesis in response to insulin, metformin or rosiglitazone is associated with increased mRNA expression of GLUT4 and peroxisomal proliferator activator receptor gamma co-activator 1.
2005 Jun
The peroxisome proliferator-activated receptor gamma ligand rosiglitazone delays the onset of inflammatory bowel disease in mice with interleukin 10 deficiency.
2005 Mar
Comparison of pioglitazone with other antidiabetic drugs for associated incidence of liver failure: no evidence of increased risk of liver failure with pioglitazone.
2005 Mar
Rosiglitazone increases indexes of stearoyl-CoA desaturase activity in humans: link to insulin sensitization and the role of dominant-negative mutation in peroxisome proliferator-activated receptor-gamma.
2005 May
Fatty acids and expression of adipokines.
2005 May 30
Trialkyltin compounds bind retinoid X receptor to alter human placental endocrine functions.
2005 Oct
Patents

Sample Use Guides

Start at 4 mg daily in single or divided doses; do not exceed 8 mg daily.
Route of Administration: Oral
Rosiglitazone treatment (5 uM) prevents NO and prostacyclin overproduction by inhibiting microparticles-induced iNOS and COX-2 expression.
Substance Class Chemical
Created
by admin
on Thu Jul 06 17:15:47 UTC 2023
Edited
by admin
on Thu Jul 06 17:15:47 UTC 2023
Record UNII
533QLZ62ZS
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ROSIGLITAZONE FUMARATE
Common Name English
2,4-THIAZOLIDINEDIONE, 5-((4-(2-(METHYL-2-PYRIDINYLAMINO)ETHOXY)PHENYL)METHYL)-, (2E)-2-BUTENEDIOATE (1:1)
Systematic Name English
Code System Code Type Description
FDA UNII
533QLZ62ZS
Created by admin on Thu Jul 06 17:15:48 UTC 2023 , Edited by admin on Thu Jul 06 17:15:48 UTC 2023
PRIMARY
CAS
403647-10-9
Created by admin on Thu Jul 06 17:15:48 UTC 2023 , Edited by admin on Thu Jul 06 17:15:48 UTC 2023
PRIMARY
PUBCHEM
6537720
Created by admin on Thu Jul 06 17:15:48 UTC 2023 , Edited by admin on Thu Jul 06 17:15:48 UTC 2023
PRIMARY
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