Leriglitazone (Hydroxypioglitazone) hydrochloride, a metabolite of pioglitazone. Leriglitazone (Hydroxypioglitazone) hydrochloride PioOH is a PPARγ agonist, stabilizes the PPARγ activation function-2 (AF-2) co-activator binding surface and enhances co-activator binding, affording slightly better transcriptional efficacy. Leriglitazone (Hydroxypioglitazone) hydrochloride binds to the PPARγ C-terminal ligand-binding domain (LBD) with a Ki of 1.2 μM，Leriglitazone induces transcriptional efficacy of the PPARγ (LBD) with an EC50 of 680 nM[1].
H-Trp-Glu-OH is a selective, reversible and cell-permeable PPARγ with a Kd of ~8 µM. H-Trp-Glu-OH might be developed as a possible lead compound in diabetes research[1].
Anti-NASH agent 1 (compound 3d)，a derivative of Elafibranor (HY-16737)，is a potent agonist of PPAR-α/δ，targeting to nonalcoholic steatohepatitis (NASH). Anti-NASH agent 1 (3-10 mg/kg; 4 weeks) improves hyperlipidemia，liver fat degeneration and liver inflammation in Methionine-choline deficiency (MCD) induced NASH mice model. Anti-NASH agent 1 shows low liver toxicity and potent liver protection effect[1].
Rosiglitazone (BRL 49653) potassium is an orally active selective PPARγ agonist (EC50: 60 nM, Kd: 40 nM). Rosiglitazone potassium is a TRPC5 activator (EC50: 30 μM) and TRPM3 inhibitor. Rosiglitazone potassium can be used in the research of obesity and diabetes, senescence, ovarian cancer[1][2][4][7].
Fmoc-leucine-d10 is the deuterium labeled Fmoc-leucine. Fmoc-leucine is a selective PPARγ modulator. Fmoc-leucine activates PPARγ with a lower potency but a similar maximal efficacy than rosiglitazone. Fmoc-leucine improves insulin sensitivity in normal, diet-induced glucose-intolerant, and in diabetic db/db mice. Fmoc-leucine has a lower adipogenic activity[1].
4β-Hydroxywithanolide E, isolated from Physalis peruviana L., inhibits adipocyte differentiation of 3T3-L1 cells through modulation of mitotic clonal expansion. 4β-Hydroxywithanolide E is an adipogenesis inhibitor and inhibits PPARγ, C/EBPα, and the adipocyte-specific molecule aP2 mRNA expression[1].
Mifobate (SR-202) is a potent and specific PPARγ antagonist. Mifobate (SR-202) selectively inhibits Thiazolidinedione (TZD)-induced PPARγ transcriptional activity (IC50=140 μM). Mifobate (SR-202) does not affect basal or ligand-stimulated transcriptional activity of PPARα, PPARβ, or the farnesoid X receptor (FXR). Mifobate (SR-202) shows antiobesity and antidiabetic effects[1].
Leriglitazone (Hydroxypioglitazone), a metabolite of pioglitazone.Leriglitazone (Hydroxypioglitazone) PioOH is a PPARγ agonist, stabilizes the PPARγ activation function-2 (AF-2) co-activator binding surface and enhances co-activator binding, affording slightly better transcriptional efficacy.Leriglitazone (Hydroxypioglitazone) binds to the PPARγ C-terminal ligand-binding domain (LBD) with Ki of 1.2 μM，induces transcriptional efficacy of the PPARγ (LBD) with EC50 of 680 nM[1].
PPARγ agonist 3 (Compound 18a) is a potent and selective agonist of PPARγ. PPARγ agonist 3 is not cytotoxic neither on non-resistant nor on resistant cells. PPARγ agonist 3 exerts antitumor potency only in combination with Imatinib[1].
Rosiglitazone-d3 (BRL 49653-d3) is the deuterium labeled Rosiglitazone. Rosiglitazone (BRL 49653) is a selective, orally active PPARγ agonist with EC50s of 30 nM, 100 nM and 60 nM for PPARγ1, PPARγ2, and PPARγ, respectively. Rosiglitazone binds to PPARγ with a Kd of approximately 40 nM. Rosiglitazone is also an activator of TRPC5 (EC50=~30 μM) and an inhibitor of TRPM3[1][2][3][4].
CDDO-Im (CDDO-imidazolide) is an activator of Nrf2 and PPAR, with Kis of 232 and 344 nM for PPARα and PPARγ.
Gancaonin L is an isoflavone, that can be isolated from Glycyrrhiza glabra roots. Gancaonin L exhibits significant PPAR-γ ligand-binding activity. Gancaonin L can be used for anti-diabetes and anti-obesity research[1].
Clofibrate is an agonist of PPAR, with EC50s of 50 μM, ∼500 μM for murine PPARα and PPARγ, and 55 μM, ∼500 μM for human PPARα and PPARγ, respectively.
Muraglitazar 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 (EC50 = 320 nM) and PPARγ(EC50 = 110 nM)[1].
Bilobetin, an active component of Ginkgo biloba, can reduce blood lipids and improve the effects of insulin. Bilobetin ameliorated insulin resistance, increased the hepatic uptake and oxidation of lipids, reduced very-low-density lipoprotein triglyceride secretion and blood triglyceride levels, enhanced the expression and activity of enzymes involved in β-oxidation and attenuated the accumulation of triglycerides and their metabolites in tissues. Bilobetin also increased the phosphorylation, nuclear translocation and activity of PPARα accompanied by elevated cAMP level and PKA activity[1].
Fmoc-leucine-13C6,15N is a 15N-labeled and 13C-labled Fmoc-leucine. Fmoc-leucine is a selective PPARγ modulator. Fmoc-leucine activates PPARγ with a lower potency but a similar maximal efficacy than rosiglitazone. Fmoc-leucine improves insulin sensitivity
Glabrone is an isoflavone isolated from Glycyrrhiza glabra roots. Glabrone exhibits anti-influenza activity and significant PPAR-γ ligand-binding activity[1][2].
Ophiopogonin D, isolated from the tubers of Ophiopogon japonicus, is a rare naturally occurring C29 steroidal glycoside[1]. Ophiopogonin D is a CYP2J3 inducer that significantly inhibits Ang II induced NF-κB nuclear translocation, IκBα down-regulation, intracellular Ca2+ overload and activation of pro-inflammatory cytokines by increasing the expression of CYP2J2/EETs and PPARα in human umbilical vein endothelial cells (HUVECs). Ophiopogonin D has been used to treat inflammatory and cardiovascular diseases for thousands of years[2].
Leriglitazone-d4 is deuterium labeled Leriglitazone. Leriglitazone (Hydroxypioglitazone), a metabolite of pioglitazone.Leriglitazone (Hydroxypioglitazone) PioOH is a PPARγ agonist, stabilizes the PPARγ activation function-2 (AF-2) co-activator binding surface and enhances co-activator binding, affording slightly better transcriptional efficacy.Leriglitazone (Hydroxypioglitazone) binds to the PPARγ C-terminal ligand-binding domain (LBD) with Ki of 1.2 μM，induces transcriptional efficacy of the PPARγ (LBD) with EC50 of 680 nM[1].
PPARα/γ agonist 2 is an orally active PPARα full agonist and PPARγ partial agonist. PPARα/γ agonist 2 activates PPARα and PPARγ with EC50 values of 0.95 μM and 0.91 μM respectively. PPARα/γ agonist 2 is also a PTP1B inhibitor. PPARα/γ agonist 2 is an anti-diabetic agent[1].
NXT629 is a potent, selective, and competitive PPAR-α antagonist, with an IC50 of 77 nM for human PPARα, shows high selectivity over other nuclear hormone receptor, such as PPARδ, PPARγ, ERβ, GR and TRβ, IC50s are 6.0, 15, 15.2, 32.5 and >100 μM, respectively[1]. NXT629 has potent anti-tumor activity and inhibits experimental metastasis of cancer cell in animal models[2].
AMG131 (INT131), a potent and highly selective PPARγ partial agonist, binds to PPARγ and displaces Rosiglitazone with a Ki of ~10 nM. AMG131 can be used for research of type-2 diabetes mellitus (T2DM)[1][2].
PPARγ-IN-2 (Compound 5a) is a PPARγ inhibitor. PPARγ-IN-2 inhibits TG accumulation in 3T3-L1 preadipocytes (EC50: 0.106 μM). PPARγ-IN-2 inhibits high-cholesterol diet (HFC)-induced obesity and related metabolic syndrome, and reduces lipid accumulation in adipose tissue[1].
GW0742 is a high affinity PPAR β/δ agonist with an IC50 of 1 nM for human PPARδ, and EC50s of 1 nM, 1.1 μM and 2 μM for human PPARδ, PPARα, and PPARγ, respectively.
T3D 959 (DB-959) is a potent, brain penetrant, orally active dual PPARδ/PPARγ agonist with EC50 of 19/297 nM, respectively; prevents STZ-induced neurotoxicity, and shows clear therapeutic and neuroprotective effects in an established model of sporadic AD. Alzheimer Disease Phase 2 Clinical
Fenofibric acid-d6 (FNF acid-d6) is the deuterium labeled Fenofibric acid. Fenofibric acid, an active metabolite of fenofibrate, is a PPAR activitor, with EC50s of 22.4 µM, 1.47 µM, and 1.06 µM for PPARα, PPARγ and PPARδ, respectively; Fenofibric acid also inhibits COX-2 enzyme activity, with an IC50 of 48 nM.
LJ570 is a PPARα/PPARγ dual agonist with EC50s of 1.05 and 0.12 μM, respectively[1].
VCE-004.8, a semi-synthetic multitarget cannabinoquinoid, is a specific PPARγ and CB2 receptor dual agonist with potent anti-inflammatory activity[1]. VCE-004.8 inhibits prolyl-hydroxylases (PHDs) and activates the HIF pathway. VCE-004.8 attenuates adipogenesis and prevents diet-induced obesity[2].
Tibesaikosaponin V (TKV) is a triterpene diglycoside, which can be isolated from the methanol extract of the roots of Bupleurum chinense DC.. Tibesaikosaponin V inhibits lipid accumulation and triacylglycerol content occurred without cytotoxicity to adipocytes. Tibesaikosaponin V suppresses the mRNA expression of nuclear transcription factors, such as peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα). Tibesaikosaponin V inhibits 3T3-L1 preadipocyte differentiation. Tibesaikosaponin V can be used fro research of obesity and its associated metabolic disorders[1].