human pparα

Tesaglitazar is a potent and selective peroxide PPARα γ receptor dual agonist with a more potent affinity for PPARγ than PPARα, The EC50 values for rat PPARα and human PPARα were 13.4 μM and 3.6 μM, respectively, and 0.2 μM for rat PPARγ and human PPARγ. Tesaglitazar induced DNA synthesis and fibrosarcoma formation in rat subcutaneous mesenchymal cells.

LY518674 (LY-674) decreases triglycerides and increases HDL-C and is used for the treatment of atherosclerosis. LY518674 is an effective and selective PPARα agonist (EC50: 42 nM for human PPARα).

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.

Aleglitazar (R1439) (R1439) is a potent dual PPARα γ agonist, with IC50s of 38 nM and 19 nM for human PPARa and PPARγ, respectively. Aleglitazar can be used for the research of type II diabetes.

Muraglitazar (BMS-298585) is a PPAR α γ dual agonist for the treatment of type 2 diabetes and associated dyslipidemia. Muraglitazar shows potent activity in vitro at human PPARα and PPARγ with EC50 of 320 nM and 110 nM respectively.

Bezafibrate (BM15075) is an antilipemic agent that lowers CHOLESTEROL and TRIGLYCERIDES. It decreases LOW-DENSITY LIPOPROTEINS and increases HIGH-DENSITY LIPOPROTEINS.

Clofibrate (Clofibrato) is an aryloxyisobutyric acid derivate with antihyperlipidemic activity.

GW 7647 is an effective and highly selective PPARα agonist, the EC 50 values of human PPARα, PPARγ and PPARδ receptors are 6,1100 and 6200 nM, respectively. GW 7647 can reduce the production of nitric oxide in macrophages and has lipid-lowering and anti-inflammatory properties in the body.

GW0742 (GW610742) is an effective and specific PPARδ agonist (EC50: 1 nM 1.1 μM 2 μM, for human PPARδ α γ).

CUDA is an effective soluble cyclohydrolase inhibitor with IC50 of 11.1 nM and 112 nM for mouse sEH and human sEH, respectively. CUDA selectively increases the activity of peroxisome proliferator-activated receptor (PPAR) alpha. CUDA may be valuable for the study of cardiovascular diseases.

NXT629 is a selective and highly efficient PPAR-α antagonist with anticancer activity. It inhibits PPARδ, PPARγ, Erβ, GR, and TRβ and can be used in research on ovarian cancer and melanoma.

Oleoylethanolamide (N-Oleoylethanolamide) is a high affinity endogenous agonist of PPAR-α.

AVE-8134 is an agonist of PPARα. For human and rodent PPARα receptor, the EC50 values are 100 and 3000 nM, respectively.

Compound 11, a selective PPARδ agonist, demonstrates an EC50 of 20 nM, indicating its high affinity for PPARδ receptors. This compound efficiently reduces levels of nitric oxide (NO), as well as the pro-inflammatory cytokines TNFα and IL-6 in LPS-stimulated RAW264.7 cells via the NF-κB pathway, showcasing its anti-inflammatory properties. Additionally, Compound 11 exhibits remarkable stability in human liver microsomes and plasma. It significantly ameliorates foot edema induced by Carrageenan, displaying favorable pharmacokinetic properties with a bioavailability of approximately 100%.

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.

TZD18, a novel PPAR alpha gamma dual agonist, inhibits cell growth and induces apoptosis in human glioblastoma T98G cells.

BMS-711939 is a potent and specific peroxisome proliferator-activated receptor (PPARα) agonist that has demonstrated excellent efficacy and safety in vivo in preclinical studies with an EC50 of 4 nM for PPARα in humans.

CP-868388 free base (CP-868388) is an orally active, potent and selective PPARα agonist with hypolipidemic and anti-inflammatory activity for the study of dyslipidemia.

Panduratin A is a natural chalcone derivative with inhibitory activity against MMP-9 in human oral epidermoid carcinoma KB cells; inhibitory activity against the NS3 protease of DENV-2 (Ki=25 μM); significant cytotoxicity against human androgen-independent prostate cancer cells PC-3 and DU-145; and also able to activate the LKB1-AMPK- PPARα δ signaling pathway and enhance the oxidative capacity of myocyte mitochondria.

Peroxisome proliferator-activated receptors (PPARs) α, δ, γ are ligand-activated nuclear transcription factors involved in the regulation of energy homeostasis as well as insulin sensitivity and glucose metabolism. Pharmacologies of PPARδ receptor agonists, though relatively obscure, have recently been reported to elevate high-density lipoprotein (HDL) cholesterol and lower plasma triglyceride (TG) levels in obese insulin resistant rhesus monkeys. CAY10592 is a full PPARδ agonist (EC50 = 30 nM) in a fatty acid oxidation assay of rat L6 muscle cells with desirable oral pharmacokinetic properties. In a transactivation assay using human PPAR receptors, CAY10592 acts as a selective partial PPARδ agonist (EC50 = 53 nM) with no effect on PPARα or PPARγ activity up to 30 μM. Chronic treatment of high fat fed ApoB100/CETP-transgenic mice with CAY10592 at a dose of 20 mg/kg increases HDL levels, decreases LDL and TG levels, and improves insulin sensitivity.

9(Z),11(E)-Conjugated linoleic acid is an isomer of linoleic acid that has been found in beef and milk fat.1It binds to peroxisome proliferator-activated receptor α (PPARα; IC50= 140 nM) and activates the receptor in a reporter assay using COS-1 cells expressing mouse PPARα when used at a concentration of 100 μM.29(Z),11(E)-Conjugated linoleic acid inhibits TNF-α-inducedGLUT4expression and increases insulin-stimulated glucose transport in 3T3-L1 adipocytes.3Dietary administration of 9(Z)11(E)-conjugated linoleic acid reduces serum fasting glucose, insulin, and triglyceride levels and decreases white adipose tissue macrophage infiltration inob/obmice. It also increases body weight gain and body fat in weanling mice.4[Matreya, LLC. Catalog No. 1278] 1.Shultz, T.D., Chew, B.P., Seaman, W.R., et al.Inhibitory effect of conjugated dienoic derivatives of linoleic acid and β-carotene on the in vitro growth of human cancer cellsCancer Lett.63(2)125-133(1992) 2.Moya-Camarena, S.Y., Heuvel, J.P.V., Blanchard, S.G., et al.Conjugated linoleic acid is a potent naturally occurring ligand and activator of PPARαJ. Lipid Res.40(8)1426-1433(1999) 3.Moloney, F., Toomey, S., Noone, E., et al.Antidiabetic effects of cis-9, trans-11-conjugated linoleic acid may be mediated via anti-inflammatory effects in white adipose tissueDiabetes56(3)574-582(2007) 4.Pariza, M.W., Park, Y., and Cook, M.E.The biologically active isomers of conjugated linoleic acidProg. Lipid Res.40(4)283-298(2001)

20-carboxy Arachidonic acid (20-COOH-AA) is the major metabolite of 20-HETE that is produced in renal tubular epithelial, endothelial, and microvascular smooth muscle cell cultures. This ω-oxidation conversion can take place using purified alcohol dehydrogenases three and four or by microsomes containing recombinant human CYP4F3B. Like 20-HETE, 20-COOH-AA inhibits ion transport in the kidneys. It also produces vasorelaxation of porcine coronary microvessels constricted with endothelin. 20-COOH-AA binds to isolated ligand binding domains of peroxisome proliferator-activated receptor α (PPARα) (Kd = 0.87 ± 0.12 μM) and PPARγ (Kd = 1.7 ± 0.5 μM), and is a dual activator of PPARα and PPARγ in a transiently transfected COS-7 cell reporter system.

20-HEPE, a metabolite of eicosapentaenoic acid, is formed via ω-oxidation of EPA by cytochrome P450 (CYP) ω-oxidases, including human CYP4F3B. It activates peroxisome proliferator-activated receptor α (PPARα) in COS-7 cells expressing a luciferase reporter at a concentration of 10 μM. 20-HEPE also activates murine transient receptor potential vanilloid receptor 1 (mTRPV1) in vitro but lacks antinociceptive activity in rats.