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

Details

Stereochemistry RACEMIC
Molecular Formula C18H19N3O3S.ClH
Molecular Weight 393.888
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ROSIGLITAZONE HYDROCHLORIDE

SMILES

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

InChI

InChIKey=XRSCTTPDKURIIJ-UHFFFAOYSA-N
InChI=1S/C18H19N3O3S.ClH/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;/h2-9,15H,10-12H2,1H3,(H,20,22,23);1H

HIDE SMILES / InChI

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 ( + / - )

Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Effects of fibrate compounds on expression of plasminogen activator inhibitor-1 by cultured endothelial cells.
1999 Jun
PPARalpha activation by Wy 14643 induces transactivation of the rat UCP-1 promoter without increasing UCP-1 mRNA levels and attenuates PPARgamma-mediated increases in UCP-1 mRNA levels induced by rosiglitazone in fetal rat brown adipocytes.
1999 Oct 22
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
Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.
2000 Mar
Synthesis and biological activity of L-tyrosine-based PPARgamma agonists with reduced molecular weight.
2001 Dec 17
A novel potent antagonist of peroxisome proliferator-activated receptor gamma blocks adipocyte differentiation but does not revert the phenotype of terminally differentiated adipocytes.
2001 Jul
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
In vivo myocardial protection from ischemia/reperfusion injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone.
2001 Nov 20
Novel genes regulated by the insulin sensitizer rosiglitazone during adipocyte differentiation.
2002 Apr
Unique ability of troglitazone to up-regulate peroxisome proliferator-activated receptor-gamma expression in hepatocytes.
2002 Jan
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.
2002 Jan 11
Troglitazone inhibits both post-glutamate neurotoxicity and low-potassium-induced apoptosis in cerebellar granule neurons.
2002 Jan 11
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size.
2002 Jul
Antidiabetic thiazolidinediones inhibit collagen synthesis and hepatic stellate cell activation in vivo and in vitro.
2002 Jun
Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation.
2002 Jun
AZ 242, a novel PPARalpha/gamma agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats.
2002 Nov
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
Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes.
2003 Dec
Rosiglitazone produces insulin sensitisation by increasing expression of the insulin receptor and its tyrosine kinase activity in brown adipocytes.
2003 Dec
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
Rosiglitazone and retinoic acid induce uncoupling protein-1 (UCP-1) in a p38 mitogen-activated protein kinase-dependent manner in fetal primary brown adipocytes.
2003 Jan 3
PPARgamma ligands induce prostaglandin production in vascular smooth muscle cells: indomethacin acts as a peroxisome proliferator-activated receptor-gamma antagonist.
2003 Oct
Induction of apoptosis by mono(2-ethylhexyl)phthalate (MEHP) in U937 cells.
2003 Oct 15
A phase II trial with rosiglitazone in liposarcoma patients.
2003 Oct 20
Rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2, ligands of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma), reduce ischaemia/reperfusion injury of the gut.
2003 Sep
Rosiglitazone inhibits the insulin-mediated increase in PAI-1 secretion in human abdominal subcutaneous adipocytes.
2003 Sep
Rosiglitazone prevents the impairment of human islet function induced by fatty acids: evidence for a role of PPARgamma2 in the modulation of insulin secretion.
2004 Apr
[Anti-hypertensive effect of rosiglitazone in non-diabetic essential hypertension].
2004 Dec
Peroxisome proliferator-activated receptor gamma ligands suppress liver carcinogenesis induced by diethylnitrosamine in rats.
2004 Dec 1
Bone is a target for the antidiabetic compound rosiglitazone.
2004 Jan
Evidence for a potent antiinflammatory effect of rosiglitazone.
2004 Jun
Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone.
2004 Nov
Rosiglitazone upregulates caveolin-1 expression in THP-1 cells through a PPAR-dependent mechanism.
2004 Nov
Rosiglitazone treatment improves insulin regulation and dyslipidemia in type 2 diabetic cynomolgus monkeys.
2004 Sep
Altered adipokine response in murine 3T3-F442A adipocytes treated with protease inhibitors and nucleoside reverse transcriptase inhibitors.
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
Chaperone proteins involved in troglitazone-induced toxicity in human hepatoma cell lines.
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
Rosiglitazone induces interleukin-1 receptor antagonist in interleukin-1beta-stimulated rat synovial fibroblasts via a peroxisome proliferator-activated receptor beta/delta-dependent mechanism.
2005 Mar
The peroxisome proliferator-activated receptor gamma ligand rosiglitazone delays the onset of inflammatory bowel disease in mice with interleukin 10 deficiency.
2005 Mar
Thiazolidinediones inhibit proliferation of microvascular and macrovascular cells by a PPARgamma-independent mechanism.
2005 Mar
The influence of adiponectin gene polymorphism on the rosiglitazone response in patients with type 2 diabetes.
2005 May
Mechanism of the anti-inflammatory effect of thiazolidinediones: relationship with the glucocorticoid pathway.
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
Peroxisome proliferator-activated receptor-gamma ligands suppress fibronectin gene expression in human lung carcinoma cells: involvement of both CRE and Sp1.
2005 Sep
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 17:00:57 UTC 2023
Edited
by admin
on Thu Jul 06 17:00:57 UTC 2023
Record UNII
S3055SS582
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ROSIGLITAZONE HYDROCHLORIDE
WHO-DD  
Common Name English
2,4-THIAZOLIDINEDIONE, 5-((4-(2-(METHYL-2-PYRIDINYLAMINO)ETHOXY)PHENYL)METHYL)-, MONOHYDROCHLORIDE
Common Name English
2,4-THIAZOLIDINEDIONE, 5-((4-(2-(METHYL-2-PYRIDINYLAMINO)ETHOXY)PHENYL)METHYL)-, HYDROCHLORIDE (1:1)
Systematic Name English
Rosiglitazone hydrochloride [WHO-DD]
Common Name English
Code System Code Type Description
SMS_ID
300000005242
Created by admin on Thu Jul 06 17:00:57 UTC 2023 , Edited by admin on Thu Jul 06 17:00:57 UTC 2023
PRIMARY
EPA CompTox
DTXSID90432078
Created by admin on Thu Jul 06 17:00:57 UTC 2023 , Edited by admin on Thu Jul 06 17:00:57 UTC 2023
PRIMARY
CAS
302543-62-0
Created by admin on Thu Jul 06 17:00:57 UTC 2023 , Edited by admin on Thu Jul 06 17:00:57 UTC 2023
PRIMARY
CAS
637339-19-6
Created by admin on Thu Jul 06 17:00:57 UTC 2023 , Edited by admin on Thu Jul 06 17:00:57 UTC 2023
SUPERSEDED
FDA UNII
S3055SS582
Created by admin on Thu Jul 06 17:00:57 UTC 2023 , Edited by admin on Thu Jul 06 17:00:57 UTC 2023
PRIMARY
PUBCHEM
9865387
Created by admin on Thu Jul 06 17:00:57 UTC 2023 , Edited by admin on Thu Jul 06 17:00:57 UTC 2023
PRIMARY
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