Highly selective peroxisome proliferator-activated receptor δ (PPARδ) modulator demonstrates improved safety profile compared to GW501516

Lagu, Bharat; Kluge, Arthur F.; Goddeeris, Matthew M.; Tozzo, Effie; Fredenburg, Ross A.; Chellur, Shekar; Senaiar, Ramesh S.; Jaleel, Mahaboobi; Babu, D. Ravi Krishna; Tiwari, Nirbhay Kumar; Takahashi, Taisuke; Patane, Michael A.

doi:10.1016/j.bmcl.2017.11.006

Cited by 10 publications

(13 citation statements)

References 15 publications

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“…The clinical development of PPARβ/δ agonists has been unsuccessful to date, and GW501516 remains a banned metabolic modulator by the World Anti-Doping Agency. Pharmaco-equivalents with better safety profiles, however, are still heavily researched [ 135 , 136 ].…”

Section: Regulation Of Ppars During Physical Exercisementioning

confidence: 99%

An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors

Phua

Wong

Liao

et al. 2018

IJMS

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Skeletal muscle comprises 30–40% of the total body mass and plays a central role in energy homeostasis in the body. The deregulation of energy homeostasis is a common underlying characteristic of metabolic syndrome. Over the past decades, peroxisome proliferator-activated receptors (PPARs) have been shown to play critical regulatory roles in skeletal muscle. The three family members of PPAR have overlapping roles that contribute to the myriad of processes in skeletal muscle. This review aims to provide an overview of the functions of different PPAR members in energy homeostasis as well as during skeletal muscle metabolic disorders, with a particular focus on human and relevant mouse model studies.

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Section: Regulation Of Ppars During Physical Exercisementioning

confidence: 99%

An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors

Phua

Wong

Liao

et al. 2018

IJMS

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“…Yet, in the present study, Cardarine was shown to reduce oxidative stress and attenuate obesity, which otherwise may activate inflammatory pathways and promote tumorigenesis (Reuter et al, 2010). Compound 1 examined by Lagu et al is a more selective PPAR-δ agonist than GW501516 that appears to exhibit an improved safety profile (Lagu et al, 2018). Thus, further research on GW501516 and similar PPAR-δ agonists are required as some benefits may outweigh impeding risks, especially in the context of metabolic syndrome-like conditions.…”

Section: Journal Ofmentioning

confidence: 62%

Cardarine (GW501516) Effects on Improving Metabolic Syndrome

Park

Kim

2021

JOHSK

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The present study hypothesized that treatment with GW501516 (a selective PPAR-δ agonist) lowers lipids by increasing fatty acid oxidation without adverse effects on oxidative stress. Caucasian men (age 18-50 years, n=18) were randomly assigned to treatment with GW501516, GW590735, or placebo for two weeks while residing in a clinical research facility. A meal tolerance test, skeletal muscle biopsy, and blood/breath sampling were conducted. The study reported that treatment with GW501516 ameliorated multiple metabolic abnormalities associated with metabolic syndrome including oxidative stress, obesity, dyslipidemia, and insulin resistance, all while increasing fatty acid oxidation. Notably, no adverse effects were reported. However, the restricted living conditions and/or diets that the participants were subjected to likely do not resemble their normal lifestyle. Therefore, the beneficial effects of GW501516 on metabolic health observed in the study should further be investigated in a real-life setting. During participant recruitment, the use of dietary supplements were minimally considered, thereby increasing the risk for confounding effects on the metabolic parameters assessed in the study. Also, recruiting a larger and more diverse population would allow for a more detailed analysis that may benefit a broader range of people (i.e., examining the effects of GW501516 in certain ethnic groups or with/without exercise programs). Additional research on GW501516 and other PPAR-δ agonists is encouraged since it appears that this class of drugs can ameliorate multiple metabolic syndrome features. Future studies should consider additional metrics relevant to metabolic syndrome such as C-reactive protein, cortisol, and homocysteine.

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“…This is also due to the lack of literature. Given the toxicity of GW501516 in animal models, 4 it is obvious that no controlled study will be implemented to address the previously mentioned issues, which have emerged for interpreting the hair findings. This is simply ethically not acceptable.…”

Section: Resultsmentioning

confidence: 99%

“…Rapidly, 3 GlaxoSmithKline and Ligand developed GW‐501516, an agonist for the potential treatment of dyslipemia. The drug reached phase II clinical trials but was discontinued in 2007 due to induction of intestinal adenoma in rats, and other highly selective PPAR‐δ with an improved safety profile were proposed 4 …”

Section: Introductionmentioning

confidence: 99%

Testing for GW501516 (cardarine) in human hair using LC/MS–MS and confirmation by LC/HRMS

Kintz

Ameline

Gheddar

et al. 2020

Drug Testing and Analysis

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GW501516, also known as GW‐1516 or cardarine and endurobol, is a peroxisome proliferator‐activated receptor delta (PPAR‐δ) agonist. Activation of the receptor will increase fat‐burning capacity and muscle production, as it changes the body's fuel preference from glucose to lipids. GW501516 has no therapeutic use, but can be abused for performance‐enhancing purposes using the oral route, at dosages of 10 to 20 mg per day, for 6 to 8 weeks. Both athletes and amateurs can abuse GW501516 as the drug can be easily obtained via the Internet. Since January 2009, the list of prohibited substances and methods of doping as established by the World Anti‐Doping Agency includes GW‐501516, first as a gene doping substance and now in the S4.5 Metabolic modulators class. It is prohibited at all times. Using LC/MS–MS and confirmation by LC/HRM, after methanol incubation of 20 mg with ultrasound for 1 hour, GW501516 was identified in the hair of a male abuser at 32 and 22 pg/mg in 2 × 2 cm segments. The result is the first evidence that this compound with a carboxylic acid function is incorporated in human hair.

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Highly selective peroxisome proliferator-activated receptor δ (PPARδ) modulator demonstrates improved safety profile compared to GW501516

Cited by 10 publications

References 15 publications

An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors

An aPPARent Functional Consequence in Skeletal Muscle Physiology via Peroxisome Proliferator-Activated Receptors

Cardarine (GW501516) Effects on Improving Metabolic Syndrome

Testing for GW501516 (cardarine) in human hair using LC/MS–MS and confirmation by LC/HRMS

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