CP-868388 is a potent PPAR-alpha agonist The orally administered CP-868388 is well tolerated. It has been very useful in acute preclinical models for treating dyslipidemia.

15-deoxy-Δ12,14-Prostaglandin J2 (15d-PGJ2) is a cyclopentanone prostaglandin and the agonist of endogenous PPAR gamma ligand, that is formed via the elimination of two molecules of water of prostaglandin D2. 15d-PGJ2 possesses anti-inflammatory effects. Experiments with animal models revealed, that 15d-PGJ2 may represent a potential therapeutic strategy in rheumatoid arthritis. Besides, 15d-PGJ2, given either systemically or locally in mice can control ongoing asthma pathological abnormalities, including eosinophil and neutrophil infiltration, mucus exacerbation, and lung remodeling triggered by ovalbumin. It was suggested, that potential exists to exploit 15d-PGJ2 as a therapeutic agent in asthma. It is known, the determination of individual prostaglandins, including 15d-PGJ2 in urine samples could improve the understanding of particular prostaglandins species under various physiological and pathological conditions. Recently was suggested the sensitive method for determination of 15d-PGJ2 and its application in human plasma samples of patients with diabetes.

15-Ketoprostaglandin E2 (15-keto PGE2) is a metabolite of prostaglandin E2 (PGE2) with reduced biological activity, which then by the action of prostaglandin reductase 2 (PTGR2) transforms into 13,14-dihydro-15-keto-PGE2, s a secondary metabolite without biological activity. Some experiments have shown that exists the therapeutic potential by targeting PTGR2/15-keto-PGE2 in pancreatic cancer. Besides, it is known, that 15-keto-PGE2 has higher affinity to the prostaglandin EP2 receptor than to the EP4 receptor. Some experiments also have revealed the key signaling cascade: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH)/15-keto-PGE2-mediated activation of PPARγ and p21(WAF1/Cip1) in the regulation of the hepatocarcinogenesis and tumor progression.

Gymnemic acid II is a glycoside isolated from the leaves of Gymnema sylvestre (Asclepiadaceae), it has being shown to be a glucose uptake inhibitor and to have a potent antidiabetic activity. Gymnemic acids are triterpene glycosides that selectively suppress taste responses to various sweet substances in humans.

Formononetin, an isoflavone, derived from Astragalus membranaceus, possesses the potential to reduce obesity and associated metabolic disorders. Formononetin displays estrogenic properties and induces angiogenesis activities. It regulates adipocyte thermogenesis as a partial PPARγ agonist and produces proangiogenesis effects through estrogen receptor alpha (ERα)-enhanced ROCK-II signaling pathways, by direct binding to the ligand-binding domain (LBD) of ERα. Besides, was shown, that formononetin inhibits HMGB1 release by decreasing HMGB1 acetylation via upregulating SIRT1 in a PPARδ-dependent manner and the identification of this process may help to treat inflammation-related disorders.

N-(Fluorenyl-9-methoxycarbonyl)leucine (NPC 15199) is an organic compound that demonstrates antiinflammatory effects. NPC 15199 and other N-(9-fluorenylmethoxycarbonyl)-protected amino acids are demonstrated to block recruitment of neutrophils into inflammatory lesions and to inhibit T-cell activation in vitro, and are classified as leumedins. N-(Fluorenyl-9-methoxycarbonyl)leucine is described to act as a chemically distinct ligand and modulator of PPARγ (peroxisome proliferator-activated receptor γ). N-(Fluorenyl-9-methoxycarbonyl)leucine is demonstrated to increase intracellular Ca2+ and to mobilize Ca2+ stores in human bladder female transitional cancer (BFTC) cells.

Bisphenol A diglycidyl ether (BADGE) is a ligand for peroxisome proliferator-activated receptor gamma (PPARgamma); in addition, this compound can antagonize the ability of agonist ligands such as rosiglitazone to activate the transcriptional and adipogenic action of this receptor. The elevation of BADGE concentration in epoxy resins-coated aluminium tubes poses a risk of developing contact dermatitis to patients sensitized to epoxy resins.

Cinnamaldehyde is one of the active compounds found in cinnamon. It was reported that cinnamaldehyde has anti-diabetic, anti-cancer, antimicrobial and anti-inflammatiry activity. Cinnamon is a common prescription compound in traditional Chinese medicine and it is used as a dietary supplement all over the world. Cinnamon dietary supplement Cinnamonforce (min. 35% cinnamaldehyde) was tested in phase II clinical trials and demonstrated therapeutic activity in patients with type 2 diabetes. The mechanism of cinnamaldehyde possibly involves the activation of PPAR gamma/delta receptors. Cinnamaldehyde is partially metabolized into cinnamic acid in the stomach and small intestine, and is almost completely metabolized into cinnamic acid in the liver. Cinnamic acid is believed to be the active metabolite, which is responsible for anti-diabetic properties of cinnamaldehyde.

Rosiglitazone acts as a highly selective and potent agonist at peroxisome proliferator activated receptors (PPAR) in target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. It is FDA approved for the treatment of as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Inhibitors of CYP2C8 (e.g., gemfibrozil) may increase rosiglitazone levels; inducers of CYP2C8 (e.g., rifampin) may decrease rosiglitazone levels. Common adverse reactions include edema, weight gain, and headache.

Magnolol is a small polyphenolic molecule with low toxicity that is isolated from the herb genus Magnolia. In preclinical experiments, magnolol was found to have anti-oxidative, anti-inflammatory, anti-tumorigenic, anti-diabetic, anti-microbial, anti-neurodegenerative and anti-depressant properties. Magnolol is a dual agonist targeting both nuclear receptors retinoic X receptor α (RXRα) and peroxisome proliferator activated receptor γ (PPARγ). These proteins function potently in metabolic diseases and are both important targets for anti-diabetic drugs. In addition, was made a suggestion, that magnolol might exert antiepileptic activity by acting at the GABAA/benzodiazepine receptor complex. Magnolol might be of benefit to the treatment of refractory Candida infection. In addition, it might be a candidate as an agent for the prevention of bone disorders such as osteoporosis. It is known, that the accumulation of oxygen-free radicals and activation of neutrophils are strongly implicated as important pathophysiological mechanisms mediating myocardial ischemia/reperfusion injury. It has been proven that various antioxidants have cardioprotective effects, including magnolol. Its properties were studied in the rat model of myocardial ischemia/reperfusion injury.