rosiglitazone

Rosiglitazone (BRL49653) is a PPARγ agonist, TRPC5 activator, and TRPM3 inhibitor with oral activity. Rosiglitazone is also a hypoglycemic agent and a thiazolidinedione insulin sensitizer.

Rosiglitazone hydrochloride (BRL-49653 HCl) is a blood glucose-lowering drugs, stimulating insulin secretion by binding to the PPAR receptors in fat cells.

Rosiglitazone maleate (BRL 49653) is the maleate salt of rosiglitazone, an orally-active thiazolidinedione with antidiabetic properties and potential antineoplastic activity.

N-desmethyl Rosiglitazone is a major metabolite of rosiglitazone , a potent and selective PPARγ ligand present in formulations that have been used to treat type 2 diabetes. Rosiglitazone is metabolized by the cytochrome P450 (CYP) isoform CYP2C8 to form N-desmethyl rosiglitazone.

Rosiglitazone (BRL 49653) potassium, a potent and selective PPARγ agonist (EC 50: 60 nM, Kd: 40 nM) administered orally, also acts as an activator of TRPC5 (EC 50: 30 μM) and an inhibitor of TRPM3. Widely used in research, it has shown promise in investigating obesity, diabetes, senescence, and ovarian cancer [1] [2] [4] [7].

1. ISOGINKGETIN (4',4'''-Dimethylamentoflavone), a compound derived from the leaves of Ginkgo biloba, to up-regulate adiponectin secretion with potency comparable to that of rosiglitazone, a known modulator of adiponectin production. 2. Isoginkgetin has anti-tumor activity, the mechanistic basis is splicing inhibition , thus, pre-mRNA splicing inhibitors may represent a novel avenue for development of new anti-cancer agents.3. Isoginkgetin can inhibit tumor cell invasion by regulating phosphatidylinositol 3-kinase Akt-dependent matrix metalloproteinase-9 expression. 4. Isoginkgetin (0.3mg kg ip for 3d) can reduce the level of O2·- in plasma and erythroeyte and sometimes increase the activity of SOD in anoxic rats, the action being stronger than aspirin.

DS-6930 is an potent and selective PPAR γ Agonists with EC50 of 41 nM. DS-6930 can effectively reduce plasma glucose (PG) level, and has less PPARγ-related adverse effects compared with Rosiglitazone. DS-6930 has research value in diabetes.

The peroxisome proliferator-activated receptors (PPARs) are lipid-activated transcription factors often used as drug targets for the treatment of metabolic disorders. CAY10573 is a PPAR agonist that displays potent binding at PPARα, γ, and δ with IC50 values of 113, 50, and 223 nM, respectively. It potently transactivates PPARα, γ, and δ with EC50 values of 8, 70, and 500 nM, respectively. CAY10573 demonstrates stronger binding and functional activity for PPARγ than the antidiabetic compound rosiglitazone (IC50 = 92 nM; EC50 = 220 nM).

Cajanin has potential hypolipidemic effects,possibly via up-regulating the ABCA1 protein expression,subsequently resulting in increased macrophage cholesterol efflux and RCT, it can significantly improve basal glucose uptake in HepG2 cells, its improving effect is concentration dependent, it exhibits effects stronger than that of rosiglitazone, which has been used as an antidiabetic drug.

2-Hydroxy-1-Methoxyaporphine can inhibit CYP2D6 activity, it also increase the glucose consumption significantly as rosiglitazone.

Oxidized low-density lipoprotein (oxLDL) particles contain low molecular weight species which promote the differentiation of monocytes via the nuclear receptor PPARγ. One of these substances was recently isolated and purified from oxLDL, and identified as azelaoyl PAF. Azelaoyl PAF is a potent PPARγ agonist which competes for the thiazolidinedione binding site. Azelaoyl PAF is more potent than 15-deoxy-δ12,14-prostaglandin J2, and equipotent with rosiglitazone as a ligand for this receptor.

Resveratrol-3-O-sulfate is a metabolite of resveratrol . In U-937 cells stimulated with LPS, resveratrol-3-O-sulfate (1 μM) decreases the expression of IL-1α, IL-1β, and IL-6 by 61.2, 76.6, and 42.2%, respectively, and decreases the release of TNF-α and IL-6 to similar levels as resveratrol. It has antioxidant activity in a Trolox assay, dose-dependently decreases growth of Caco-2 colorectal adenocarcinoma cells when used at concentrations ranging from 10 to 100 μM, and induces apoptosis at concentrations of 25 and 50 μM. Resveratrol-3-O-sulfate also displaces rosiglitazone from the outer mitochondrial protein mitoNEET (IC50 = 3.36 μM for the human protein), indicating that it binds to the thiazolidine-2,4-dione (TZD) binding pocket.