ppar-δ

Imiglitazar (TAK559) is a potent PPAR-β/δ receptor agonist with hypoglycemic effects.

Indeglitazar (PPM 204) is orally available pan-agonist of PPAR (PPAR subtypes alpha (α), delta (δ), and gamma (γ)).

Seladelpar (MBX 8025) has been used in trials studying the treatment of Hyperlipidemia.

Seladelpar lysine, a selective PPAR-δ agonist, is used for the therapy of Homozygous Familial Hypercholesterolemia (HoFH).

Anti-NASH Agent 1 (Compound 3d), derived from Elafibranor, serves as a strong PPAR-α/δ agonist aimed at treating nonalcoholic steatohepatitis (NASH). At dosages of 3-10 mg/kg over four weeks, this compound ameliorates hyperlipidemia, liver fat degeneration, and inflammation in a methionine-choline deficiency (MCD)-induced NASH mouse model, exhibiting minimal hepatotoxicity while providing substantial hepatic protection [1].

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).

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.

Pparδ agonist 1 is an agonist of PPAR-δ(EC50 of 5.06 nM).

Bocidelpar is a modulator of PPARδ with an EC50 of 7.80 nM and improves mitochondrial biogenesis and function in Duchenne Muscular Dystrophy muscle cells.

Elafibranor (GFT505) is an agonist of the peroxisome proliferator-activated receptor-α (PPAR-α) and peroxisome proliferator-activated receptor-δ (PPAR-δ) with EC50 values of 45 and 175 nM, respectively.

PT-S58 is a PPAR β/δ full antagonist, and a derivative of GSK0660. PT-S58 has a three-fold higher affinity for the receptor than GSK0660 and is a potent inhibitor of agonist-induced target gene expression. PT-S58 are effective on PPRE-independent functions of PPARβ/δ. Unlike GSK0660, PT-S58 blocks the recruitment co-repressor molecules such as SMRT.