Rosiglitazone-d₄  (Synonyms: BRL 49653-d₄)

Rosiglitazone-d₄ is deuterated labeled Rosiglitazone (HY-17386). Rosiglitazone (BRL 49653) is an orally active selective PPARγ agonist (EC₅₀: 60 nM, K_d: 40 nM). Rosiglitazone is an TRPC5 activator (EC₅₀: 30 μM) and TRPM3 inhibitor. Rosiglitazone can be used in the research of obesity and diabetes, senescence, ovarian cancer^[1][2][4][7].

Stable heavy isotopes of hydrogen, carbon, and other elements have been incorporated into drug molecules, largely as tracers for quantitation during the drug development process. Deuteration has gained attention because of its potential to affect the pharmacokinetic and metabolic profiles of drugs^[1].
Rosiglitazone (0.1-10 μM, 72 h) results in pluripotent C3H10T1/2 stem cell differentiation to adipocytes^[2].
Rosiglitazone (1 μM, 24 h) activates PPARγ, which binds to NF-α1 promoter to activate gene transcription in neurons^[4].
Rosiglitazone (1 μM, 24 h) protects Neuro2A cells and hippocampal neurons against oxidative stress, and up-regulates BCL-2 expression in an NF-α1-dependent manner^[4].
Rosiglitazone (0.01-100 μM, 15 min) inhibits TRPM3 with IC₅₀ values of 9.5 and 4.6 μM against nifedipine- and PregS-evoked activity respectively^[5].
Rosiglitazone (0.5-50 μM, 7 days) inhibits ovarian cancer cell proliferation^[8].
Rosiglitazone (5 μM, 7 days) suppresses Olaparib (HY-10162) induced alterations of cellular senescence and promotes apoptosis in A2780 and SKOV3 cells^[8].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Rosiglitazone (oral administration, 5 mg/kg, daily for 8 weeks) decreases the serum glucose in diabetic rats^[6].
Rosiglitazone (intraperitoneal injection, 3 mg/kg/day) ameliorates airway inflammation induced by cigarette smoke via inhibiting the M1 macrophage polarization by activating PPARγ and RXRα in male Wistar rats^[7].
Rosiglitazone (intraperitoneal injection, 10 mg/kg, once every 2 days) inhibits subcutaneous ovarian cancer growth in A2780 and SKOV3 mouse subcutaneous xenograft models^[8].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

361.45

C₁₈H₁₅D₄N₃O₃S

1132641-21-4

122320-73-4

O=C(N1)SC(CC2=CC=C(OC([2H])([2H])C([2H])([2H])N(C)C3=NC=CC=C3)C=C2)C1=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216.  [Content Brief]

  [2]. Lehmann JM, et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem. 1995 Jun 2;270(22):12953-6.  [Content Brief]

  [3]. Haoshen Feng, et al. Rosiglitazone ameliorated airway inflammation induced by cigarette smoke via inhibiting the M1 macrophage polarization by activating PPARγ and RXRα. Int Immunopharmacol. 2021 Aug;97:107809.  [Content Brief]

  [4]. Willson TM, et al. The structure-activity relationship between peroxisome proliferator-activated receptor gamma agonism and the antihyperglycemic activity of thiazolidinediones. J Med Chem. 1996 Feb 2;39(3):665-8.  [Content Brief]

  [5]. Zehua Wang, et al. Rosiglitazone ameliorates senescence and promotes apoptosis in ovarian cancer induced by olaparib. Cancer Chemother Pharmacol. 2020 Feb;85(2):273-284.  [Content Brief]

  [6]. Thouennon E, et al. Rosiglitazone-activated PPARγ induces neurotrophic factor-α1 transcription contributing to neuroprotection. J Neurochem. 2015 Aug;134(3):463-70.  [Content Brief]

  [7]. Majeed Y, et al. Rapid and contrasting effects of rosiglitazone on transient receptor potential TRPM3 and TRPC5 channels. Mol Pharmacol. 2011 Jun;79(6):1023-30.  [Content Brief]

  [8]. Ateyya H, et al. Beneficial effects of rosiglitazone and losartan combination in diabetic rats. Can J Physiol Pharmacol. 2018 Mar;96(3):215-220.  [Content Brief]