In vitro metabolism study of a black market product containing SARM LGD‐4033

Geldof, Lore; Pozo, Óscar J.; Lootens, Leen; Morthier, Wouter; Eenoo, Peter Van; Deventer, Koen

doi:10.1002/dta.1930

Cited by 37 publications

(54 citation statements)

References 27 publications

(58 reference statements)

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“…33 A study of healthy young men 35 proved that LGD-4033 is safe, well-tolerated, has favorable pharmacokinetic profile with a prolonged elimination half-life (24-36 hours), and shows lean body mass increase. 42 The in vitro (in human) liver microsomes metabolites 34,40 as well as by electrochemical conversion/microbial degradation metabolites of While its use is unofficially approved and it is not yet manufactured by a pharmaceutical company, many websites make LGD-4033 widely available 36-38 and studies have reported its detection in black market products.…”

mentioning

confidence: 99%

Human in vivo metabolism study of LGD‐4033

Fragkaki

Sakellariou

Kiousi

et al. 2018

Drug Testing and Analysis

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Selective androgen receptor modulators (SARMs) are an emerging class of therapeutics targeted to cachexia, sarcopenia, and hypogonadism treatment. LGD-4033 is a SARM which has been included on the Prohibited List annually released by the World Anti-Doping Agency (WADA). The aim of the present work was the investigation of the metabolism of LGD-4033 in a human excretion study after administration of an LGD-4033 supplement, the determination of the metabolites' excretion profiles with special interest in the determination of its long-term metabolites, and the comparison of the excretion time of the phase I and phase II metabolites. The results were also compared to those derived from previous LGD-4033 studies concerning both in vitro and in vivo experiments. Supplement containing LGD-4033 was administered to one human male volunteer and urine samples were collected up to almost 21 days. Analysis of the hydrolyzed (with β-glucuronidase) as well as of the non-hydrolyzed samples was performed using liquid chromatography-high resolution mass spectrometry (LC-HRMS) in negative ionization mode and revealed that, in both cases, the two isomers of the dihydroxylated metabolite (M5) were preferred target metabolites. The glucoconjugated parent LGD-4033 and its gluco-conjugated metabolites M1 and M2 can be also considered as useful target analytes in non-hydrolyzed samples. The study also presents two trihydroxylated metabolites (M6) identified for the first time in human urine; one of them was recently reported in an LGD-4033 metabolism study in horse urine and plasma. KEYWORDS human doping, LGD-4033, liquid chromatography-mass spectrometry, SARM, selective androgen receptor modulator

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confidence: 99%

Human in vivo metabolism study of LGD‐4033

Fragkaki

Sakellariou

Kiousi

et al. 2018

Drug Testing and Analysis

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“…9,28 The product ions observed in the spectra of M5 (Table 1) This metabolite has previously been reported following an in vitro study of LGD-4033 with human microsomes, and was later identified in human urine.…”

Section: Identification Of In Vitro Metabolitesmentioning

confidence: 86%

“…Due to the ease of availability over the internet, the misuse of LGD-4033 has already been reported in the human sports arena, 8 highlighting the need for routine methods that allow the best possible detection of these novel substances in doping control laboratories. 9,10 Numerous other SARMs have also been studied in the human. As a result, studies have been carried out utilising human liver microsomes to investigate the human metabolism of LGD-4033 products in vitro.…”

Section: -Yl)-2-(trifluoromethyl)-benzonitrile) Is a Member Of A CLmentioning

confidence: 99%

Investigation of the metabolism of the selective androgen receptor modulator LGD‐4033 in equine urine, plasma and hair following oral administration

Cutler¹,

Viljanto²,

Hincks³

et al. 2020

Drug Testing and Analysis

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LGD-4033 is one of a number of selective androgen receptor modulators (SARMs) that are being developed by the pharmaceutical industry to provide the therapeutic benefits of anabolic androgenic steroids, without the less desirable side effects.Though not available therapeutically, SARMs are available for purchase online as supplement products. The potential for performance enhancing effects associated with these products makes them a significant concern with regards to doping control in sports. The purpose of this study was to investigate the metabolism of LGD-4033 in the horse following oral administration, in order to identify the most appropriate analytical targets for doping control laboratories. LGD-4033 was orally administered to two Thoroughbred horses and urine, plasma and hair samples were collected and analysed for parent drug and metabolites. LC-HRMS was used for metabolite identification in urine and plasma. Eight metabolites were detected in urine, five of which were excreted only as phase II conjugates, with the longest detection time being observed for di-and tri-hydroxylated metabolites. The parent compound could only be detected in urine in the conjugated fraction. Seven metabolites were detected in plasma along with the parent compound where mono-hydroxylated metabolites provided the longest duration of detection. Preliminary investigations with hair samples using LC-MS/MS analysis indicated the presence of trace amounts of the parent compound and one of the mono-hydroxylated metabolites. In vitro incubation ofLGD-4033 with equine liver microsomes was also performed for comparison, yielding 11 phase I metabolites. All of the metabolites observed in vivo were also observed in vitro.

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“…As the best studied SARM, GTx‐024 has been evaluated in phase III clinical trials for the treatment of muscle wasting in patients with non‐small‐cell lung cancer and is now under phase II trials for stress urinary incontinence and AR + TNBC etc (NCT02658448, NCT02971761). LGD‐4033 is an oral SARM under development by Ligand Pharmaceuticals Inc (LGND) . In a phase I clinical trial, it appeared to be safe and increased the lean body mass of healthy young male in a short period without changing the value of PSA .…”

Section: Ar and Anabolic Deficienciesmentioning

confidence: 99%

A magic drug target: Androgen receptor

Zhou

Pang

et al. 2018

Medicinal Research Reviews

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Androgen receptor (AR) is closely associated with a group of hormone‐related diseases including the cancers of prostate, breast, ovary, pancreas, etc and anabolic deficiencies such as muscle atrophy and osteoporosis. Depending on the specific type and stage of the diseases, AR ligands including not only antagonists but also agonists and modulators are considered as potential therapeutics, which makes AR an extremely interesting drug target. Here, we at first review the current understandings on the structural characteristics of AR, and then address why and how AR is investigated as a drug target for the relevant diseases and summarize the representative antagonists and agonists targeting five prospective small molecule binding sites at AR, including ligand‐binding pocket, activation function‐2 site, binding function‐3 site, DNA‐binding domain, and N‐terminal domain, providing recent insights from a target and drug development view. Further comprehensive studies on AR and AR ligands would bring fruitful information and push the therapy of AR relevant diseases forward.

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In vitro metabolism study of a black market product containing SARM LGD‐4033

Cited by 37 publications

References 27 publications

Human in vivo metabolism study of LGD‐4033

Human in vivo metabolism study of LGD‐4033

Investigation of the metabolism of the selective androgen receptor modulator LGD‐4033 in equine urine, plasma and hair following oral administration

A magic drug target: Androgen receptor

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