ROSIGLITAZONE

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C18H19N3O3S
Molecular Weight	357.427
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=YASAKCUCGLMORW-UHFFFAOYSA-N

InChI=1S/C18H19N3O3S/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)

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	( + / - )

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021071s051lbl.pdf
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

Targets

Primary Target	Pharmacology	Condition	Potency
Peroxisome proliferator-activated receptor gamma 111 Target ID: CHEMBL235 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021071s051lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/10764590	Agonist 2678		40.0 nM [Kd]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021071s051lbl.pdf	Primary		Approved 8429	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 1999

C_max

Value	Dose	Co-administered	Analyte	Population
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

Value	Dose	Co-administered	Analyte	Population
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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

Dose	Population	Adverse 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

AE	Significance	Dose	Population
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

Title	Date	PubMed
Asymmetry in the PPARgamma/RXRalpha crystal structure reveals the molecular basis of heterodimerization among nuclear receptors.	2000 Mar	10882139
Troglitazone inhibits mitogenic signaling by insulin in vascular smooth muscle cells.	2000 May	10813377
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	11397815
Synthesis and biological activity of L-tyrosine-based PPARgamma agonists with reduced molecular weight.	2001 Dec 17	11720854
Troglitazone and rosiglitazone induce apoptosis of vascular smooth muscle cells through an extracellular signal-regulated kinase-independent pathway.	2001 Feb	11218074
Fatty-acyl-CoA thioesters inhibit recruitment of steroid receptor co-activator 1 to alpha and gamma isoforms of peroxisome-proliferator-activated receptors by competing with agonists.	2001 Jan 15	11139385
Troglitazone treatment increases plasma vascular endothelial growth factor in diabetic patients and its mRNA in 3T3-L1 adipocytes.	2001 May	11334422
Novel genes regulated by the insulin sensitizer rosiglitazone during adipocyte differentiation.	2002 Apr	11916924
Unique ability of troglitazone to up-regulate peroxisome proliferator-activated receptor-gamma expression in hepatocytes.	2002 Jan	11752099
Fibrate and statin synergistically increase the transcriptional activities of PPARalpha/RXRalpha and decrease the transactivation of NFkappaB.	2002 Jan 11	11779144
Troglitazone inhibits both post-glutamate neurotoxicity and low-potassium-induced apoptosis in cerebellar granule neurons.	2002 Jan 11	11750908
Ligands of the peroxisome proliferator-activated receptors (PPAR-gamma and PPAR-alpha) reduce myocardial infarct size.	2002 Jul	12087064
Peroxisome proliferator-activated receptor agonists inhibit inflammatory edema and hyperalgesia.	2002 Jun	12083418
Comparative effects of thiazolidinediones on in vitro P450 enzyme induction and inhibition.	2003 Apr	12642470
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.	2003 Jan 1	12464242
A yeast two-hybrid technology-based system for the discovery of PPARgamma agonist and antagonist.	2004 Dec 15	15556564
Reduction of intracellular cholesterol accumulation in THP-1 macrophages by a combination of rosiglitazone and atorvastatin.	2004 Jul 1	15183127
PPAR(gamma) agonist rosiglitazone improves vascular function and lowers blood pressure in hypertensive transgenic mice.	2004 Mar	14744930
Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.	2004 May	15089784
Hepatic lipase mRNA, protein, and plasma enzyme activity is increased in the insulin-resistant, fructose-fed Syrian golden hamster and is partially normalized by the insulin sensitizer rosiglitazone.	2004 Nov	15504970
Comparison of the effects of pioglitazone and rosiglitazone on macrophage foam cell formation.	2004 Oct 22	15381068
Rosiglitazone treatment improves insulin regulation and dyslipidemia in type 2 diabetic cynomolgus monkeys.	2004 Sep	15334371
Altered adipokine response in murine 3T3-F442A adipocytes treated with protease inhibitors and nucleoside reverse transcriptase inhibitors.	2005	15865214
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	15665514
Effect of rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 on bleomycin-induced lung injury.	2005 Feb	15684285
Mechanism of the anti-inflammatory effect of thiazolidinediones: relationship with the glucocorticoid pathway.	2005 May	15684043
Trialkyltin compounds bind retinoid X receptor to alter human placental endocrine functions.	2005 Oct	15941851

Patents

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 Dec 15 16:18:29 GMT 2023` Edited by `admin` on `Fri Dec 15 16:18:29 GMT 2023`
Record UNII	05V02F2KDG
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

ROSIGLITAZONE

Official Name

English

ROSIGLIZOLE

Brand Name

English

BRL-49653

Code

English

NSC-758698

Code

English

ROSIGLITAZONE [MI]

Common Name

English

rosiglitazone [INN]

Common Name

English

ROSIGLITAZONE [EMA EPAR]

Common Name

English

REZULT

Brand Name

English

TDZ-01

Code

English

ROSIGLITAZONE [VANDF]

Common Name

English

2,4-THIAZOLIDINEDIONE, 5-((4-(2-(METHYL-2-PYRIDINYLAMINO)ETHOXY)PHENYL)METHYL)-

Systematic Name

English

ROSIGLITAZONE [MART.]

Common Name

English

ROSIGLITAZONE [IARC]

Common Name

English

ROSVEL

Brand Name

English

GAUDIL

Brand Name

English

5-((4-(2-(METHYL-2-PYRIDINYLAMINO)ETHOXY)PHENYL)METHYL)-2,4-THIAZOLIDINEDIONE

Systematic Name

English

ROSIGLITAZONE [HSDB]

Common Name

English

Rosiglitazone [WHO-DD]

Common Name

English

5-(4-(2-(N-METHYL-N-(2-PYRIDINYL)AMINO)ETHOXY)BENZYL)-2,4-THIAZOLIDINEDIONE

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C98241