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Details

Stereochemistry EPIMERIC
Molecular Formula C18H19N3O3S.C4H6O6
Molecular Weight 507.514
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of Rosiglitazone tartrate

SMILES

O[C@H]([C@@H](O)C(O)=O)C(O)=O.CN(CCOC1=CC=C(CC2SC(=O)NC2=O)C=C1)C3=CC=CC=N3

InChI

InChIKey=ADQQXOGMNHWLRB-LREBCSMRSA-N
InChI=1S/C18H19N3O3S.C4H6O6/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;5-1(3(7)8)2(6)4(9)10/h2-9,15H,10-12H2,1H3,(H,20,22,23);1-2,5-6H,(H,7,8)(H,9,10)/t;1-,2-/m.1/s1

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 C4H6O6
Molecular Weight 150.0868
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

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.

CNS Activity

Originator

Approval Year

1999
159
Targets

Targets

Primary TargetPharmacologyConditionPotency
Agonist
2662
 40.0 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8360
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
DRUG LABEL
https://www.fda.gov/media/75754/download
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
DRUG LABEL
https://www.fda.gov/media/75754/download
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
DRUG LABEL
https://www.fda.gov/media/75754/download
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
DRUG LABEL
https://www.fda.gov/media/75754/download
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
DRUG LABEL
https://www.fda.gov/media/75754/download
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
DRUG LABEL
https://www.fda.gov/media/75754/download
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:
https://pubmed.ncbi.nlm.nih.gov/18503774
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:
https://pubmed.ncbi.nlm.nih.gov/18503774
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:
https://pubmed.ncbi.nlm.nih.gov/18503774
Page: p.105
20 mg single, oral
Overdose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/25390127
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:
https://pubmed.ncbi.nlm.nih.gov/25390127
Page: p.73,74
Disc. AE: Macular edema...
AEs leading to
discontinuation/dose reduction:
Macular edema
Sources:
https://pubmed.ncbi.nlm.nih.gov/25390127
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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:
https://pubmed.ncbi.nlm.nih.gov/18503774
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:
https://pubmed.ncbi.nlm.nih.gov/18503774
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:
https://pubmed.ncbi.nlm.nih.gov/18503774
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:
https://pubmed.ncbi.nlm.nih.gov/18503774
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:
https://pubmed.ncbi.nlm.nih.gov/18503774
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:
https://pubmed.ncbi.nlm.nih.gov/18503774
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:
https://pubmed.ncbi.nlm.nih.gov/18503774
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:
https://pubmed.ncbi.nlm.nih.gov/18503774
Page: p.105
Macular edema Disc. AE
20 mg single, oral
Overdose
Dose: 20 mg
Route: oral
Route: single
Dose: 20 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/25390127
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:
https://pubmed.ncbi.nlm.nih.gov/25390127
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
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:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
Page: p.1
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021071s031lbl.pdf
Page: p.1
PubMed

PubMed

TitleDatePubMed
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
Activation of peroxisome proliferator-activated receptor gamma suppresses nuclear factor kappa B-mediated apoptosis induced by Helicobacter pylori in gastric epithelial cells.
2001 Aug 17
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
In vivo myocardial protection from ischemia/reperfusion injury by the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone.
2001 Nov 20
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
Divergent effects of selective peroxisome proliferator-activated receptor-gamma 2 ligands on adipocyte versus osteoblast differentiation.
2002 Jun
Evaluation of liver function in type 2 diabetic patients during clinical trials: evidence that rosiglitazone does not cause hepatic dysfunction.
2002 May
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
Lipid metabolome-wide effects of the PPARgamma agonist rosiglitazone.
2002 Nov
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
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
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
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
Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation.
2003 Jul
Regulation of retinoic acid receptor beta expression by peroxisome proliferator-activated receptor gamma ligands in cancer cells.
2003 Jul 1
AhR- and ERK-dependent pathways function synergistically to mediate 2,3,7,8-tetrachlorodibenzo-p-dioxin suppression of peroxisome proliferator-activated receptor-gamma1 expression and subsequent adipocyte differentiation.
2003 May 15
A phase II trial with rosiglitazone in liposarcoma patients.
2003 Oct 20
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
Bone is a target for the antidiabetic compound rosiglitazone.
2004 Jan
PPAR(gamma) agonist rosiglitazone improves vascular function and lowers blood pressure in hypertensive transgenic mice.
2004 Mar
Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.
2004 May
Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro.
2004 Oct
Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation.
2004 Oct 22
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
Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury.
2005 Feb
Chaperone proteins involved in troglitazone-induced toxicity in human hepatoma cell lines.
2005 Feb
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
Rosiglitazone causes bone loss in mice by suppressing osteoblast differentiation and bone formation.
2005 Mar
Effects of metformin and rosiglitazone treatment on insulin signaling and glucose uptake in patients with newly diagnosed type 2 diabetes: a randomized controlled study.
2005 May
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
Mechanism of the anti-inflammatory effect of thiazolidinediones: relationship with the glucocorticoid pathway.
2005 May
Fatty acids and expression of adipokines.
2005 May 30
Patents

Patents

06515132
8
JP2002543077A
8
JP2004536047A
24
JP2008195625A
8
JP2011252007A
8
JP4365554B2
22
JP4741458B2
8

Sample Use Guides

In Vivo Use Guide
Start at 4 mg daily in single or divided doses; do not exceed 8 mg daily.
Route of Administration: Oral
In Vitro Use Guide
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 Fri Jul 07 00:39:26 UTC 2023
Edited
by admin
on Fri Jul 07 00:39:26 UTC 2023
Record UNII
3DQ9JH6CDA
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
Rosiglitazone tartrate
Common Name English
Rosiglitazone tartrate [WHO-DD]
Common Name English
2,4-Thiazolidinedione, 5-[[4-[2-(methyl-2-pyridinylamino)ethoxy]phenyl]methyl]-, (2R,3R)-2,3-dihydroxybutanedioate (1:1)
Systematic Name English
Code System Code Type Description
FDA UNII
3DQ9JH6CDA
Created by admin on Fri Jul 07 00:39:27 UTC 2023 , Edited by admin on Fri Jul 07 00:39:27 UTC 2023
PRIMARY
PUBCHEM
9849118
Created by admin on Fri Jul 07 00:39:27 UTC 2023 , Edited by admin on Fri Jul 07 00:39:27 UTC 2023
PRIMARY
CAS
397263-86-4
Created by admin on Fri Jul 07 00:39:27 UTC 2023 , Edited by admin on Fri Jul 07 00:39:27 UTC 2023
PRIMARY
SMS_ID
300000047319
Created by admin on Fri Jul 07 00:39:27 UTC 2023 , Edited by admin on Fri Jul 07 00:39:27 UTC 2023
PRIMARY
Related Record Type Details
Structure of TARTARIC ACID
PARENT -> SALT/SOLVATE
Structure of ROSIGLITAZONE
PARENT -> SALT/SOLVATE
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