mouse pparγ

Pioglitazone hydrochloride (AD 4833) is the hydrochloride salt of an orally-active thiazolidinedione with antidiabetic properties and potential antineoplastic activity.

Pioglitazone (U 72107) is an insulin sensitizing agent and thiazolidinedione indicated for the treatment of type 2 diabetes, and has been linked to rare instances of acute liver injury.

BAY-4931 is a powerful, covalent, and selective inverse-agonist of PPARγ, exhibiting an IC50 value of 0.17 nM.

PPARγ agonist16 (Compound 4G) is a PPARγ agonist that competitively binds to the ligand-binding domain (LBD) of PPARγ with an IC50 of 1790 nM. It reduces ear swelling in mouse models and exhibits antihyperglycemic activity in mice with Streptozotocin-induced diabetes.

PPARγmodulator-2 (Compound (R)-2n) is a reversible modulator of PPARγ, inhibiting the PPARγ ligand-binding domain (LBD) with an IC50 of 41 nM. It helps lower blood glucose levels, improves glucose tolerance and insulin sensitivity, and demonstrates antidiabetic activity in db db mouse models.

PPARα δ agonist 3 (Compound 8) is an orally active PPAR agonist capable of activating PPARα, PPARδ, and PPARγ, with EC50 values of 5.6 nM, 3.4 nM, and 1278 nM, respectively. It exhibits anti-cholestatic activity in mouse models of cholestatic liver disease induced by ANIT or CDCA.

LT175, a dual PPARα γ ligand, demonstrates potent insulin-sensitizing effects with reduced adipogenic properties. This orally active partial agonist targets PPARγ with EC50 values of 0.22 μm for hPPARα, 0.26 μm for mPPARα, and 0.48 μm for hPPARγ. LT175 specifically interacts with PPARγ, influencing the recruitment of coregulators, such as the cyclic-AMP response element-binding protein-binding protein and nuclear corepressor 1 (NCoR1), within a hydrophobic region known as the diphenyl pocket [1].

GW 9578 is a selective and potent PPARα agonist with potent lipid-lowering activity for the study of psoriasis, arthritis, alopecia, asthma and type I diabetes.

SR 1903 is a modulator of retinoic acid receptor-related orphan receptor γ (RORγ) and liver X receptor (LXR).1 It is an inverse agonist of RORγ (IC50 = ~100 nM in a cell-based reporter assay) and an agonist of LXR. It also binds to peroxisome proliferator-activated receptor γ (PPARγ; IC50 = 209 nM) but does not activate it. SR 1903 (10 μM) inhibits LPS-induced expression of triggering receptor expressed on myeloid cells 1 (TREM-1) in RAW 264.7 cells. It also inhibits LPS-induced expression of the LXR target genes IL-6 and IL-33 and increases expression of ABCG1, FASN, and SCD-1 in RAW 264.7 cells. SR 1903 (20 mg kg twice per day) reduces severity score in a mouse model of collagen-induced arthritis. It reduces blood glucose levels in a glucose tolerance test, serum levels of total cholesterol and LDL, body weight, and fat mass in a mouse model of high-fat diet-induced obesity.References1. Chang, M.R., Ciesla, A., Strutzenberg, T.S., et al. Unique polypharmacology nuclear receptor modulator blocks inflammatory signaling pathways. ACS Chem. Biol. 14(5), 1051-1062 (2019). SR 1903 is a modulator of retinoic acid receptor-related orphan receptor γ (RORγ) and liver X receptor (LXR).1 It is an inverse agonist of RORγ (IC50 = ~100 nM in a cell-based reporter assay) and an agonist of LXR. It also binds to peroxisome proliferator-activated receptor γ (PPARγ; IC50 = 209 nM) but does not activate it. SR 1903 (10 μM) inhibits LPS-induced expression of triggering receptor expressed on myeloid cells 1 (TREM-1) in RAW 264.7 cells. It also inhibits LPS-induced expression of the LXR target genes IL-6 and IL-33 and increases expression of ABCG1, FASN, and SCD-1 in RAW 264.7 cells. SR 1903 (20 mg kg twice per day) reduces severity score in a mouse model of collagen-induced arthritis. It reduces blood glucose levels in a glucose tolerance test, serum levels of total cholesterol and LDL, body weight, and fat mass in a mouse model of high-fat diet-induced obesity. References1. Chang, M.R., Ciesla, A., Strutzenberg, T.S., et al. Unique polypharmacology nuclear receptor modulator blocks inflammatory signaling pathways. ACS Chem. Biol. 14(5), 1051-1062 (2019).

ZLY032 is a dual agonist of free fatty acid receptor 1 (FFAR1/GPR40; EC50= 68 nM in a FLIPR assay) and peroxisome proliferator-activated receptor δ (PPARδ; EC50= 102 nM in a reporter assay).1It is selective for FFAR1 and PPARδ over PPARα and PPARγ (EC50s = >10 μM for both). ZLY032 (40 mg/kg, twice per day) reduces blood glucose levels in an oral glucose tolerance test and decreases plasma total cholesterol and triglyceride levels in theob/obmouse model of metabolic disease.2It reduces hepatic steatosis and plasma alanine transaminase (ALT) and aspartate aminotransferase (AST) levels in a mouse model of non-alcoholic steatohepatitis (NASH) induced by a methionine and choline-deficient diet at the same dose. 1.Li, Z., Chen, Y., Zhou, Z., et al.Discovery of first-in-class thiazole-based dual FFA1/PPARδ agonists as potential anti-diabetic agentsEur. J. Med. Chem.164352-365(2019) 2.Li, Z., Zhou, Z., Hu, L., et al.ZLY032, the first-in-class dual FFA1/PPARδ agonist, improves glucolipid metabolism and alleviates hepatic fibrosisPharmacol Res.159105035(2020)

Pioglitazone potassium (U 72107) is an orally active, selective agonist of peroxisome proliferator-activated receptor gamma (PPARγ), exhibiting high-affinity binding to the ligand-binding domain of PPARγ with EC50 values of 0.93 μM for human and 0.99 μM for mouse PPARγ. It has applications in diabetes research [2] [3] [4].

GSK1820795A, a telmisartan analog, functions as a selective antagonist of hGPR132a, inhibiting the activation of yeast cells that express hGPR132a by N-acylamides [1]. Additionally, it acts as an angiotensin II antagonist and a partial PPARγ agonist (compound 38) [2].

Norbixin, a carotenoid found in B. orellana, exhibits various biological activities including binding to the peroxisome proliferator-activated receptor γ (PPARγ) with a Ki of 1.15 µM in a cell-free assay. At a dosage of 47.7 mg/kg, norbixin effectively alleviates hyperglycemia, hyperinsulinemia, and insulin resistance, in addition to reducing serum lipid levels, cardiac thiobarbituric acid reactive substances (TBARS), and glutathione (GSH) in rat cardio-metabolic syndrome models. It also lowers serum levels of oxidized LDL, aortic protein oxidation, and the atherosclerotic area in a rabbit cholesterol-induced atherosclerosis model. Furthermore, norbixin, administered at 0.1 and 1 mg/kg per day, minimizes mercury-induced DNA damage in rat hepatocytes and leukocytes and prevents photoreceptor degeneration in an Abca4-/- Rdh8-/- mouse model of age-related macular degeneration (AMD).

15-deoxy-Δ12,14-Prostaglandin D2 (15-deoxy-Δ12,14-PGD2) is a PGD2 metabolite functioning as an agonist for the PGD2 receptor 2 (DP2), with a binding affinity (Ki) of 50 nM for the mouse DP2 receptor expressed in HEK293 cell membranes. It activates eosinophils with an EC50 of 8 nM and enhances the recruitment of steroid receptor coactivator-1 (SRC-1) to peroxisome proliferator-activated receptor γ (PPARγ), initiating PPARγ-mediated transcription at 5 µM concentration. Furthermore, it exhibits cytotoxicity towards L1210 murine leukemia cells with an IC50 of 0.3 µg/ml and displays weaker inhibition of ADP-induced platelet aggregation than PGD2, with an IC50 of 320 ng/ml.

YGT-31 is a PPARγ modulator with an IC50 of 1.72 μM and a Ki of 0.62 μM. It diminishes blood glucose levels and enhances insulin sensitivity in a type 2 diabetes model in db db mice by inhibiting CDK5-mediated phosphorylation of PPARγ-Ser273. Additionally, YGT-31 exhibits anti-steatotic effects in a mouse model of non-alcoholic fatty liver disease (NAFLD).

ST-CY14 is an inhibitor of the Nur77-PPARγ interaction with an EC50 of 3.15 μM. It binds to Nur77 (Kd=32 nM) to prevent its ubiquitination and degradation by PPARγ, reducing fatty acid uptake and mitochondrial respiration, and inhibiting the transcription of CD36 and FABP4. ST-CY14 suppresses proliferation and migration of MCF7 and MDA-MB-231 cancer cells and impedes tumor growth and bone metastasis in mouse models.