Darglitazone | CAS# 141200-24-0 | agonist of PPAR-γ

MedKoo Cat#: 524937 | Name: Darglitazone

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Darglitazone, also known as CP-86,325-2, is PPAR-gamma agonist. Darglitazone restores acute inflammatory responses to cerebral hypoxia-ischemia in the diabetic ob/ob mouse. Darglitazone enhanced adipogenesis and caused cancellous bone loss by increasing bone resorption and decreasing bone formation in mice. In addition, darglitazone induced cortical bone loss on the endocortical surface but increased bone formation on the periosteal surface.

Chemical Structure

Darglitazone

CAS#141200-24-0 (free)

Theoretical Analysis

MedKoo Cat#: 524937

Name: Darglitazone

CAS#: 141200-24-0 (free)

Chemical Formula: C23H20N2O4S

Exact Mass: 420.1144

Molecular Weight: 420.48

Elemental Analysis: C, 65.70; H, 4.79; N, 6.66; O, 15.22; S, 7.62

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 325.00	2 Weeks
10mg	USD 580.00	2 Weeks

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Related CAS #

141200-24-0 (free) 141683-98-9 (sodium)

Synonym

Darglitazone; CP-86325; CP86325; CP 86325;

IUPAC/Chemical Name

5-(4-(3-(5-methyl-2-phenyloxazol-4-yl)propanoyl)benzyl)thiazolidine-2,4-dione

InChi Key

QQKNSPHAFATFNQ-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H20N2O4S/c1-14-18(24-22(29-14)17-5-3-2-4-6-17)11-12-19(26)16-9-7-15(8-10-16)13-20-21(27)25-23(28)30-20/h2-10,20H,11-13H2,1H3,(H,25,27,28)

SMILES Code

O=C1NC(SC1CC2=CC=C(C=C2)C(CCC3=C(OC(C4=CC=CC=C4)=N3)C)=O)=O

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Related CAS# 141200-24-0 (Darglitazone) 141683-98-9 (Darglitazone sodium)

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Darglitazone (CP-86325), a thiazolidinedione, is a potent, selective, and orally active PPAR-γ agonist.

In vitro activity:

Since TZD have been reported to increase energy expenditure in animals, we have examined the effects of these drugs on the expression of UCP2 mRNA in cell lines representing white (3T3-L1 and 3T3-F442A) and brown (HIB-1B) adipose tissues and skeletal muscle (L6). Within 4 h of exposing these cells to 30 microM darglitazone, there was an increase in UCP2 mRNA which reached a plateau of 5-10 times the basal in about 8 h. In all cells TZDs (darglitazone, troglitazone) were more active than the predominantly PPAR alpha ligands WY-14,613 and clofibrate, or the non-selective ligand linoleic acid. These results indicate that TZDs can stimulate the expression of UCP2 gene probably via PPAR gamma and hence have the potential to increase energy expenditure in adult humans, in whom UCP2 is expressed ubiquitously. Reference: Endocrinology. 1998 Jan;139(1):428-31. https://pubmed.ncbi.nlm.nih.gov/9421444/

In vivo activity:

In this study, the actions of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist darglitazone were investigated in treating diabetes and promoting recovery after a hypoxic-ischemic (H/I) insult in the diabetic ob/ob mouse. Male ob/+ and ob/ob mice received darglitazone (1 mg/kg) for 7 days before induction of H/I. Euglycemia in the ob/ob mice was restored and maintained by 48 h of darglitazone treatment, and darglitazone-treated ob/ob mice remained normoglycemic throughout the entire experiment. Figure 2 illustrates that H/I induced a profound, transient elevation of CORT in the ob/+ mice at 4 h of recovery, which was significantly reduced by darglitazone treatment (471±65 versus 273±63 ng/mL). Darglitazone also dramatically reduced the area of infarction in the diabetic mice from 30% to 2%. After H/I, darglitazone treatment of diabetic mice resulted in significant neuroprotection associated with a complete restoration of the initial microglial response observed in control mice, as evidenced by increased TNFα, IL-1β, and bfl1 expression in the diabetic brain at 4 h of recovery. Reference: J Cereb Blood Flow Metab. 2010 Feb;30(2):352-60. https://pubmed.ncbi.nlm.nih.gov/19861974/

	Solvent	mg/mL	mM
Solubility
	DMSO	20.0	47.56
	DMF	20.0	47.56

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 420.48 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Camirand A, Marie V, Rabelo R, Silva JE. Thiazolidinediones stimulate uncoupling protein-2 expression in cell lines representing white and brown adipose tissues and skeletal muscle. Endocrinology. 1998 Jan;139(1):428-31. doi: 10.1210/endo.139.1.5808. PMID: 9421444. 2. Haugen F, Jørgensen A, Drevon CA, Trayhurn P. Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes. FEBS Lett. 2001 Oct 19;507(1):105-8. doi: 10.1016/s0014-5793(01)02968-4. PMID: 11682067. 3. Kumari R, Willing LB, Patel SD, Krady JK, Zavadoski WJ, Gibbs EM, Vannucci SJ, Simpson IA. The PPAR-gamma agonist, darglitazone, restores acute inflammatory responses to cerebral hypoxia-ischemia in the diabetic ob/ob mouse. J Cereb Blood Flow Metab. 2010 Feb;30(2):352-60. doi: 10.1038/jcbfm.2009.221. Epub 2009 Oct 28. PMID: 19861974; PMCID: PMC2949120. 4. Oakes ND, Thalén PG, Jacinto SM, Ljung B. Thiazolidinediones increase plasma-adipose tissue FFA exchange capacity and enhance insulin-mediated control of systemic FFA availability. Diabetes. 2001 May;50(5):1158-65. doi: 10.2337/diabetes.50.5.1158. PMID: 11334421.

In vitro protocol:

In vivo protocol:

1. Kumari R, Willing LB, Patel SD, Krady JK, Zavadoski WJ, Gibbs EM, Vannucci SJ, Simpson IA. The PPAR-gamma agonist, darglitazone, restores acute inflammatory responses to cerebral hypoxia-ischemia in the diabetic ob/ob mouse. J Cereb Blood Flow Metab. 2010 Feb;30(2):352-60. doi: 10.1038/jcbfm.2009.221. Epub 2009 Oct 28. PMID: 19861974; PMCID: PMC2949120. 2. Oakes ND, Thalén PG, Jacinto SM, Ljung B. Thiazolidinediones increase plasma-adipose tissue FFA exchange capacity and enhance insulin-mediated control of systemic FFA availability. Diabetes. 2001 May;50(5):1158-65. doi: 10.2337/diabetes.50.5.1158. PMID: 11334421.

1: Kumari R, Willing LB, Patel SD, Krady JK, Zavadoski WJ, Gibbs EM, Vannucci SJ, Simpson IA. The PPAR-gamma agonist, darglitazone, restores acute inflammatory responses to cerebral hypoxia-ischemia in the diabetic ob/ob mouse. J Cereb Blood Flow Metab. 2010 Feb;30(2):352-60. doi: 10.1038/jcbfm.2009.221. PubMed PMID: 19861974; PubMed Central PMCID: PMC2949120. 2: Nadanaciva S, Dykens JA, Bernal A, Capaldi RA, Will Y. Mitochondrial impairment by PPAR agonists and statins identified via immunocaptured OXPHOS complex activities and respiration. Toxicol Appl Pharmacol. 2007 Sep 15;223(3):277-87. PubMed PMID: 17658574. 3: Li M, Pan LC, Simmons HA, Li Y, Healy DR, Robinson BS, Ke HZ, Brown TA. Surface-specific effects of a PPARgamma agonist, darglitazone, on bone in mice. Bone. 2006 Oct;39(4):796-806. PubMed PMID: 16759917. 4: Aleo MD, Doshna CM, Navetta KA. Ciglitazone-induced lenticular opacities in rats: in vivo and whole lens explant culture evaluation. J Pharmacol Exp Ther. 2005 Mar;312(3):1027-33. PubMed PMID: 15523002. 5: Floyd ZE, Stephens JM. Control of peroxisome proliferator-activated receptor gamma2 stability and activity by SUMOylation. Obes Res. 2004 Jun;12(6):921-8. PubMed PMID: 15229330. 6: Zawalich WS, Tesz G, Zawalich KC. Contrasting effects of nateglinide and rosiglitazone on insulin secretion and phospholipase C activation. Metabolism. 2003 Nov;52(11):1393-9. PubMed PMID: 14624396. 7: Hoenig M, Ferguson DC. Effect of darglitazone on glucose clearance and lipid metabolism in obese cats. Am J Vet Res. 2003 Nov;64(11):1409-13. PubMed PMID: 14620778. 8: Salomonsson L, Svensson L, Pettersson S, Wiklund O, Ohlsson BG. Oxidised LDL decreases VEGFR-1 expression in human monocyte-derived macrophages. Atherosclerosis. 2003 Aug;169(2):259-67. PubMed PMID: 12921977. 9: Svensson L, Camejo G, Cabré A, Vallvé JC, Pedreño J, Norén K, Wiklund O, Hultén LM. Fatty acids modulate the effect of darglitazone on macrophage CD36 expression. Eur J Clin Invest. 2003 Jun;33(6):464-71. PubMed PMID: 12795642. 10: Granlund L, Juvet LK, Pedersen JI, Nebb HI. Trans10, cis12-conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARgamma modulator. J Lipid Res. 2003 Aug;44(8):1441-52. PubMed PMID: 12754280. 11: Aleo MD, Lundeen GR, Blackwell DK, Smith WM, Coleman GL, Stadnicki SW, Kluwe WM. Mechanism and implications of brown adipose tissue proliferation in rats and monkeys treated with the thiazolidinedione darglitazone, a potent peroxisome proliferator-activated receptor-gamma agonist. J Pharmacol Exp Ther. 2003 Jun;305(3):1173-82. PubMed PMID: 12626651. 12: López-Solache I, Marie V, Camirand A, Silva JE. Regulation of uncoupling protein-2 mRNA in L6 myotubules: II: Thyroid hormone amplifies stimulation of uncoupling protein-2 gene by thiazolidinediones and other peroxisome proliferator-activated receptor ligands in L6 myotubules: evidence for a priming effect. Endocrine. 2002 Nov;19(2):209-17. PubMed PMID: 12588052. 13: López-Solache I, Marie V, Vignault E, Camirand A, Silva JE. Regulation of uncoupling protein-2 mRNA in L6 myotubules: I: Thiazolidinediones stimulate uncoupling protein-2 gene expression by a mechanism requiring ongoing protein synthesis and an active mitogen-activated protein kinase. Endocrine. 2002 Nov;19(2):197-208. PubMed PMID: 12588051. 14: Juvet LK, Andresen SM, Schuster GU, Dalen KT, Tobin KA, Hollung K, Haugen F, Jacinto S, Ulven SM, Bamberg K, Gustafsson JA, Nebb HI. On the role of liver X receptors in lipid accumulation in adipocytes. Mol Endocrinol. 2003 Feb;17(2):172-82. PubMed PMID: 12554745. 15: Haugen F, Jørgensen A, Drevon CA, Trayhurn P. Inhibition by insulin of resistin gene expression in 3T3-L1 adipocytes. FEBS Lett. 2001 Oct 19;507(1):105-8. PubMed PMID: 11682067. 16: Oakes ND, Thalén PG, Jacinto SM, Ljung B. Thiazolidinediones increase plasma-adipose tissue FFA exchange capacity and enhance insulin-mediated control of systemic FFA availability. Diabetes. 2001 May;50(5):1158-65. PubMed PMID: 11334421. 17: Bakopanos E, Silva JE. Thiazolidinediones inhibit the expression of beta3-adrenergic receptors at a transcriptional level. Diabetes. 2000 Dec;49(12):2108-15. PubMed PMID: 11118014. 18: Aleo MD, Avery MJ, Beierschmitt WP, Drupa CA, Fortner JH, Kaplan AH, Navetta KA, Shepard RM, Walsh CM. The use of explant lens culture to assess cataractogenic potential. Ann N Y Acad Sci. 2000;919:171-87. PubMed PMID: 11083107. 19: Olsson U, Bondjers G, Camejo G. Fatty acids modulate the composition of extracellular matrix in cultured human arterial smooth muscle cells by altering the expression of genes for proteoglycan core proteins. Diabetes. 1999 Mar;48(3):616-22. PubMed PMID: 10078565. 20: Camirand A, Marie V, Rabelo R, Silva JE. Thiazolidinediones stimulate uncoupling protein-2 expression in cell lines representing white and brown adipose tissues and skeletal muscle. Endocrinology. 1998 Jan;139(1):428-31. PubMed PMID: 9421444.