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Record W4416387150 · doi:10.1002/dta.70005

Further Insights Into the Metabolism of LGD‐4033 in Human Urine. Part 2. A New Minor Metabolite With Antagonistic Activity on the Androgen Receptor Can Indicate Recent Substance Intake

2025· article· en· W4416387150 on OpenAlexfundno aff
Yiannis S. Angelis, P. Sakellariou, Annekathrin M. Keiler, Mario Thevis, Andreas Thomas, Kevin Lam, Gerhard Wolber, Ariadni Vonaparti, Sven Christian Voss, Michael Petrou, Emmanuel N. Pitsinos

Bibliographic record

VenueDrug Testing and Analysis · 2025
Typearticle
Languageen
FieldMedicine
TopicHormonal and reproductive studies
Canadian institutionsnot available
FundersWorld Anti-Doping AgencyHellenic Academic Libraries Link
KeywordsMetaboliteAndrogen receptorTransactivationIn silicoMetabolismAndrogenUrine

Abstract

fetched live from OpenAlex

ABSTRACT Using a targeted metabolic investigation approach, a new, previously undescribed metabolite, which is a pyrrole derivative of LGD‐4033, has been detected and coded as M8 . This metabolite can be detected in postadministration human urine samples up to 6 days after administration. It has also been detected in post‐administration samples, mimicking supplement contamination, after repeated 10 μg doses detectable for ≥ 120 h after administration. Given M8's structural similarity to LGD‐4033, its androgen receptor (AR) agonist/antagonist properties were studied using in silico molecular docking and functional in vitro AR transactivation assays in the PC3(AR) 2 cell model, alongside other selected LGD‐4033 metabolites. The results indicate that M8 can act as a potent AR antagonist, whereas M2c was reconfirmed as a potent AR agonist. Therefore, we propose the inclusion of M2c in ITP doping control methods, as it could be used as an LGD‐4033 alternative and may be introduced into the black market. Additionally, the detection of M8 , which is an early‐stage excreted metabolite, is valuable for estimating sample collection time relative to LGD‐4033 intake. When combined with the evaluation of other long‐term metabolites like M5b, M5a, M2c, and M2d, M8 detection can aid in distinguishing adverse analytical findings, associated abuse through regular dosing, from unintentional doping caused by certain contamination scenarios or abuse through microdosing.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.114
Threshold uncertainty score0.411

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.002
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.025
GPT teacher head0.264
Teacher spread0.239 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations1
Published2025
Admission routes1
Has abstractyes

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