GW501516, also known as Cardarine, is not a SARM but rather a selective PPARδ and AMP-K modulator developed in a collaboration between Ligand Pharmaceuticals and GlaxoSmithKline for treatment of obesity, diabetes, dyslipidemia, cholesterol imbalance, and cardiovascular disease. PPARδ and AMP-K are the same pathways activated during exercise and are involved in energy production and fatty acid metabolism. GW501516 displays high affinity for the PPARδ receptor with over 1000-fold selectivity over PPARα and PPARγ .
GW501516 – Early Clinical Trials
In 2000 and 2002 respectively, GlaxoSmithKline performed phase I clinical trials and by 2007 GW501516 had completed two phase II clinical studies and other studies related to obesity, diabetes, dyslipidemia, and cardiovascular disease . Studies in rhesus monkeys showed that cardarine increased HDL and reduced LDL indicating potential for cardiovascular improvement . Further work on GW501516 was abandoned after doses of 3mg/kg/day were shown to increase the rate of replication for cancer cells, a potential risk in administration of anabolic agents .
GW501516 And Sports
By 2009, word had spread that this compound could provide an athlete with an endurance increase for any sport. This gave rise to the use in athletics, where it is banned and as early as 2011 athletes were testing positive for GW501516 . At the Vuelta Ciclista a Costa Rica in December 2012, four Costa Rican riders tested positive for GW501516 . In 2013 Russian cyclist Valery Kaykov and Venezuelan Miguel Ubeto tested positive for GW501516 [7 ,8]. In 2014 Russian race walker Elena Lashnamova tested positive, and then in 2019 heavyweight boxer Jarrell Miller tested positive which caused the cancellation of his challenge against Anthony Joshua’s world heavyweight titles [9, 10].
GW501516 Investigational Benefits Summary:
1. Increases endurance for physical activity
2. Improves insulin sensitivity and reduces bodyfat
3. Correction of imbalanced HDL/LDL/Triglycerides
1. Oliver WR, Shenk JL, Snaith MR, Russell CS, Plunket KD, Bodkin NL, Lewis MC, Winegar DA, Sznaidman ML, Lambert MH, Xu HE, Sternbach DD, Kliewer SA, Hansen BC, Willson TM (April 2001). “A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport”. Proc. Natl. Acad. Sci. U.S.A. 98 (9): 5306–11. doi:10.1073/pnas.091021198. PMC 33205. PMID 11309497.
2. “GW501516 Glaxo Wellcome phase change I, UK”. R & D Focus Drug News. 20 November 2000.
4. Geiger LE, Dunsford WS, Lewis DJ, Brennan C, Liu KC, Newsholme SJ (2009). PS 895 – Rat carcinogenicity study with GW501516, a PPAR delta agonist (PDF). 48th Annual Meeting of the Society of Toxicology. Baltimore: Society of Toxicology. p. 105. Archived from the original (PDF) on 2015-05-04.5. Thevis M, Geyer H, Thomas A, Schänzer W (May 2011). “Trafficking of drug candidates relevant for sports drug testing: detection of non-approved therapeutics categorized as anabolic and gene doping agents in products distributed via the Internet”. Drug Test Anal. 3 (5): 331–6. doi:10.1002/dta.283. PMID 21538997.
6. Shane Stokes: Four riders each handed two year bans for use of GW501516, velonation.com 30 July 2013
7. “European champion Valery Kaykov sacked for failing drug test”. BBC. 2013-04-11. Retrieved 2013-04-11
8. “Miguel Ubeto Aponte provisionally suspended”. UCI. 2013-05-13. Archived from the original on 2013-06-28. Retrieved 2013-05-15
9. Associated Press: Doping probe launched into Russian walkers, espn.com, 11 July 2014
10. Sanctioned athletes list – 26 June 2014