LGD-2226
LGD-2226 is a distinct androgen-receptor modulator with rodent muscle, bone-strength, and sexual-behavior findings. Those studies support biological activity and some tissue selectivity, but the cited evidence contains no human efficacy or pharmacokinetic program. Results for other LGD compounds do not fill that gap.
preclinical nonsteroidal selective androgen-receptor modulator
- Also written LGD2226 or LGD 2226
- Quinolinone SARM, distinct from LGD-4033 and LGD-3303
- No cited human trial or human pharmacokinetic study
- WADA's SARM class prohibition applies in 2026
Is LGD-2226 another name for ligandrol or LGD-3303?
No. LGD-2226 is a separate quinolinone androgen-receptor modulator with its own structure, PubChem record, and preclinical program. Results for LGD-4033, also called ligandrol, and LGD-3303 cannot be assigned to it.
PubChem · LGD-2226 identity
Official chemical identity record
National Center for Biotechnology Information. PubChem CID 11560224.
The record identifies LGD-2226 with formula C14H9F9N2O, molecular weight 392.22 g/mol, CAS 328947-93-9, and UNII RI376RM5MT.
- Study design
- Chemical database record
Identity is not approval or product authentication.
Read the original sourceWang et al., human AR receptor crystal, 2006
Primary preclinical study
Wang F, Liu XQ, Li H, Liang KN, Miner JN, Hong M, Kallel EA, van Oeveren A, Zhi L, Jiang T. Structure of the ligand-binding domain (LBD) of human androgen receptor in complex with a selective modulator LGD2226. Acta crystallographica. Section F, Structural biology and crystallization communications. 2006. DOI 10.1107/s1744309106039340.
The 2.1-angstrom structure binds LGD2226 to isolated human AR ligand-binding domain, with contacts around Gln711 and Arg752. A human protein experiment is not an administered-human trial. The structure shows target binding; it cannot predict whole-body endocrine selectivity or clinical safety.
- Participants / model
- Purified human androgen-receptor ligand-binding domain
- Treatment
- LGD-2226 complex
- Study design
- X-ray crystallography
- Funding
- Industry and structural-biology collaboration
What does LGD-2226 do at the androgen receptor?
It binds and activates the androgen receptor. Crystal-structure work showed LGD-2226 in the human receptor's ligand-binding pocket, while receptor-panel and functional studies described nonaromatizable, selective agonist activity. No human tissue-safety study followed.
The 2.1-angstrom receptor complex explains molecular binding. The apparent muscle-versus-prostate separation comes from specific animal models and cannot be assumed to persist across human exposures.
Wang et al., human AR receptor crystal, 2006
Primary preclinical study
Wang F, Liu XQ, Li H, Liang KN, Miner JN, Hong M, Kallel EA, van Oeveren A, Zhi L, Jiang T. Structure of the ligand-binding domain (LBD) of human androgen receptor in complex with a selective modulator LGD2226. Acta crystallographica. Section F, Structural biology and crystallization communications. 2006. DOI 10.1107/s1744309106039340.
The 2.1-angstrom structure binds LGD2226 to isolated human AR ligand-binding domain, with contacts around Gln711 and Arg752. A human protein experiment is not an administered-human trial. The structure shows target binding; it cannot predict whole-body endocrine selectivity or clinical safety.
- Participants / model
- Purified human androgen-receptor ligand-binding domain
- Treatment
- LGD-2226 complex
- Study design
- X-ray crystallography
- Funding
- Industry and structural-biology collaboration
Miner et al. · rodent efficacy program
Preclinical cell and animal study
Miner JN, Chang W, Chapman MS, Finn PD, Hong MH, López FJ, Marschke KB, Rosen J, Schrader W, Turner R, van Oeveren A, Viveros H, Zhi L, Negro-Vilar A. Endocrinology. 2007;148(1):363-373. DOI 10.1210/en.2006-0793.
LGD-2226 acted as a selective, nonaromatizable androgen-receptor agonist in cell panels and produced muscle, bone, bone-strength, and sexual-behavior effects in androgen- or estrogen-deficient rodent models with less prostate stimulation than testosterone under tested conditions.
- Participants / model
- Cell systems and androgen- or estrogen-deficient rodent models
- Treatment
- Oral LGD-2226 with vehicle and androgen comparators
- Follow-up
- Study-specific short and multi-month rodent experiments
- Study design
- Controlled preclinical pharmacology program
- Funding
- Ligand Pharmaceuticals-associated study
The paper reports rodent surrogate and behavior outcomes; it includes no human strength, fracture, sexual-function, or safety data.
Read the original sourceWhat did the rodent program actually show?
LGD-2226 increased androgen-responsive muscle, preserved bone measures and improved mechanical bone quality in deficient rodents. Its muscle-versus-prostate separation was substantial in those assays, but has not been established in people.
In two-week castrated-rat assays with eight animals per group, levator-ani restoration occurred at much lower experimental exposure than prostate restoration. LH suppression differed from testosterone; this does not establish an absence of endocrine suppression.
Bone work included six- and sixteen-week experiments with mechanical outcomes. An earlier four-month report came from the same originator program, and possible cohort overlap prevents counting every paper as independent replication. Most authors of the broader development paper were Ligand employees.
The eight-week sexual-behavior experiment included 15 vehicle, 16 LGD-2226 and 16 fluoxymesterone rats. Every group received estradiol implants. Improved mounts, intromissions and ejaculation therefore cannot support an estrogen-independent human libido claim.
van Oeveren et al., discovery chemistry, 2006
Primary preclinical study
van Oeveren A, Motamedi M, Mani NS, Marschke KB, López FJ, Schrader WT, Negro-Vilar A, Zhi L. Discovery of 6-N,N-bis(2,2,2-trifluoroethyl)amino- 4-trifluoromethylquinolin-2(1H)-one as a novel selective androgen receptor modulator. Journal of medicinal chemistry. 2006. DOI 10.1021/jm060792t.
The originator paper, DOI 10.1021/jm060792t, identifies orally active tissue-selective 6-dialkylamino quinolinones. Vendor summaries assign compound 4m binding and potency values, but the abstract does not report those exact values, so they are not used here. The medicinal-chemistry series establishes a molecule-development program, not human dosing or selectivity.
Read the original sourceMiner et al., muscle/bone/sexual behavior, 2007
Primary preclinical study
Miner JN, Chang W, Chapman MS, Finn PD, Hong MH, López FJ, Marschke KB, Rosen J, Schrader W, Turner R, van Oeveren A, Viveros H, Zhi L, Negro-Vilar A. Endocrinology. 2007;148(1):363-373. DOI 10.1210/en.2006-0793.
Two-week castrated-rat assays used eight animals per group. Levator-ani mass reached sham values near 3 mg/kg/day; prostate restoration required roughly 100 mg/kg/day. LH suppression differed from testosterone but was not absent. Bone experiments ran for six or sixteen weeks and included mechanical strength. In the eight-week sexual-behavior study, mounts, intromissions, and ejaculation improved versus vehicle, but every group received estradiol implants. Most authors were Ligand employees, and no human outcomes were measured.
Duplicate record for Miner et al. 2007; it is not independent evidence.
Read the original sourceRosen and colleagues, early LGD2226 bone program, 2005
Primary preclinical study
Rosen J, Negro-Vilar A. Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile. Journal of musculoskeletal & neuronal interactions. 2002. PMID 15758439.
Skeletally mature orchiectomized male rats underwent four months of exposure. The paper reports suppression of increased bone turnover, maintained density, cortical bone formation and improved mechanical quality, together with levator-ani activity. The abstract does not expose complete group denominators, allocation or numerical effect estimates. The same originator program and duration overlap with later work; without cohort identifiers it should not be counted as wholly independent replication.
Abstract and bibliographic record only.
Read the original sourceHas LGD-2226 been tested in humans?
The cited records include no human administration study. ClinicalTrials.gov lists no exact-name study, and the cited papers are preclinical or analytical. They provide no human dose-response, half-life, bioavailability, benefit, adverse-event rate, or interaction profile.
ClinicalTrials.gov · no LGD-2226 study listed
Clinical trial registry
ClinicalTrials.gov records for LGD-2226 and its cited aliases.
ClinicalTrials.gov lists no study under LGD-2226 or its cited aliases. The cited literature likewise includes no human administration report or human pharmacokinetic dataset.
- Participants / model
- ClinicalTrials.gov records
- Treatment
- LGD-2226
Chinese and Russian records · no additional outcome study
Literature and registry records
Chinese and Russian literature and registry records for LGD-2226.
The cited Chinese record is an androgen-receptor crystal-structure paper and reports no administered-subject outcome. The cited Russian records are analytical mentions, reviews, and catalogs without an additional efficacy or safety study.
- Participants / model
- Chinese- and Russian-language records
What safety and interaction claims are defensible?
Androgen-receptor activation makes endocrine and reproductive effects plausible. FDA warns that marketed SARM products as a class carry cardiovascular, hepatic, sexual, fertility, and testicular concerns. No LGD-2226 human study quantifies those risks or defines interactions, contraindications, monitoring, or a safe threshold.
The class warning is context, not molecule-specific incidence. Product contamination and substitution are separate risks because the clinical program never authenticated retail LGD-2226.
FDA · SARM class warning
FDA safety communication
U.S. Food and Drug Administration, updated December 2025.
FDA states that marketed SARM bodybuilding products are unapproved drugs and describes serious cardiovascular, hepatic, reproductive, sexual, and testicular class concerns.
- Participants / model
- Consumers of marketed SARM products
- Treatment
- SARM class
- Study design
- Agency class-risk communication
- Funding
- U.S. FDA
The communication does not provide LGD-2226-specific incidence or prove a particular product's contents.
Read the original sourceIs LGD-2226 approved or allowed in tested sport?
The cited regulatory and clinical records show no approved medicine or active human program. WADA's 2026 S1.2 rule prohibits the SARM class with an open-ended list of examples. The primary papers identify LGD-2226 as a SARM.
ClinicalTrials.gov · no LGD-2226 study listed
Clinical trial registry
ClinicalTrials.gov records for LGD-2226 and its cited aliases.
ClinicalTrials.gov lists no study under LGD-2226 or its cited aliases. The cited literature likewise includes no human administration report or human pharmacokinetic dataset.
- Participants / model
- ClinicalTrials.gov records
- Treatment
- LGD-2226
WADA 2026 · SARM class applies
Official anti-doping standard
World Anti-Doping Agency. The 2026 Prohibited List, effective 1 January 2026.
Section S1.2 prohibits selective androgen-receptor modulators at all times using an including-but-not-limited-to formulation. LGD-2226 is not named individually in the list.
- Participants / model
- Athletes subject to the World Anti-Doping Code
- Follow-up
- Calendar year 2026
- Study design
- Anti-doping prohibited list
- Funding
- World Anti-Doping Agency
The class assignment follows LGD-2226's primary pharmacology; the list itself does not name it.
Read the original sourceMiner et al. · rodent efficacy program
Preclinical cell and animal study
Miner JN, Chang W, Chapman MS, Finn PD, Hong MH, López FJ, Marschke KB, Rosen J, Schrader W, Turner R, van Oeveren A, Viveros H, Zhi L, Negro-Vilar A. Endocrinology. 2007;148(1):363-373. DOI 10.1210/en.2006-0793.
LGD-2226 acted as a selective, nonaromatizable androgen-receptor agonist in cell panels and produced muscle, bone, bone-strength, and sexual-behavior effects in androgen- or estrogen-deficient rodent models with less prostate stimulation than testosterone under tested conditions.
- Participants / model
- Cell systems and androgen- or estrogen-deficient rodent models
- Treatment
- Oral LGD-2226 with vehicle and androgen comparators
- Follow-up
- Study-specific short and multi-month rodent experiments
- Study design
- Controlled preclinical pharmacology program
- Funding
- Ligand Pharmaceuticals-associated study
The paper reports rodent surrogate and behavior outcomes; it includes no human strength, fracture, sexual-function, or safety data.
Read the original sourceDo Chinese- or Russian-language records show a local human or animal study?
A human androgen-receptor crystal-structure paper involving Chinese Academy of Sciences authors shows how LGD-2226 binds to the receptor, but it contains no administered animal or human outcome. The cited Russian-language records add analytical mentions and reviews, with no new efficacy or safety data.
Chinese and Russian records · no additional outcome study
Literature and registry records
Chinese and Russian literature and registry records for LGD-2226.
The cited Chinese record is an androgen-receptor crystal-structure paper and reports no administered-subject outcome. The cited Russian records are analytical mentions, reviews, and catalogs without an additional efficacy or safety study.
- Participants / model
- Chinese- and Russian-language records
Wang et al., human AR receptor crystal, 2006
Primary preclinical study
Wang F, Liu XQ, Li H, Liang KN, Miner JN, Hong M, Kallel EA, van Oeveren A, Zhi L, Jiang T. Structure of the ligand-binding domain (LBD) of human androgen receptor in complex with a selective modulator LGD2226. Acta crystallographica. Section F, Structural biology and crystallization communications. 2006. DOI 10.1107/s1744309106039340.
The 2.1-angstrom structure binds LGD2226 to isolated human AR ligand-binding domain, with contacts around Gln711 and Arg752. A human protein experiment is not an administered-human trial. The structure shows target binding; it cannot predict whole-body endocrine selectivity or clinical safety.
- Participants / model
- Purified human androgen-receptor ligand-binding domain
- Treatment
- LGD-2226 complex
- Study design
- X-ray crystallography
- Funding
- Industry and structural-biology collaboration
Did it ever reach human development?
A Ligand SEC filing listed LGD-2226 and backups as IND-track. That establishes a development plan, not a completed human trial.
ClinicalTrials.gov lists no exact-name public trial record. Later secondary accounts say development stopped, but the cited primary records do not explain why. No human half-life or bioavailability should be borrowed from LGD-4033, ACP-105, or another SARM.
The human androgen-receptor crystal and urine-detection work establish binding and analytical methods. A human protein or urine matrix does not mean people received the compound in a treatment study.
Wang et al., human AR receptor crystal, 2006
Primary preclinical study
Wang F, Liu XQ, Li H, Liang KN, Miner JN, Hong M, Kallel EA, van Oeveren A, Zhi L, Jiang T. Structure of the ligand-binding domain (LBD) of human androgen receptor in complex with a selective modulator LGD2226. Acta crystallographica. Section F, Structural biology and crystallization communications. 2006. DOI 10.1107/s1744309106039340.
The 2.1-angstrom structure binds LGD2226 to isolated human AR ligand-binding domain, with contacts around Gln711 and Arg752. A human protein experiment is not an administered-human trial. The structure shows target binding; it cannot predict whole-body endocrine selectivity or clinical safety.
- Participants / model
- Purified human androgen-receptor ligand-binding domain
- Treatment
- LGD-2226 complex
- Study design
- X-ray crystallography
- Funding
- Industry and structural-biology collaboration
Thevis et al., anti-doping detection, 2007
Analytical identity or detection study
Thevis M, Kohler M, Maurer J, Schlörer N, Kamber M, Schänzer W. Screening for 2-quinolinone-derived selective androgen receptor agonists in doping control analysis. Rapid communications in mass spectrometry : RCM. 2007. DOI 10.1002/rcm.3247.
Four quinolinone SARMs, including LGD2226, were synthesized and characterized for urine screening. Detection limits were 0.01 to 0.2 ng/mL and recovery was 81 to 98%. The work validated an analytical method and did not administer LGD-2226 as a treatment.
Abstract only.
Read the original sourceLigand SEC development record
Official scientific or regulatory record
Ligand SEC development record. https://www.sec.gov/Archives/edgar/data/886163/000088616303000010/ligand200210k.htm
The 2002 annual report lists LGD2226/backups as IND-track with TAP rights for hormone-related indications. A company development plan is not evidence that a human trial started or completed. Later secondary accounts report discontinuation, but the cited primary records do not explain why.
Company regulatory filing.
Read the original sourceClinicalTrials.gov · no exact-name study
Clinical trial registry
ClinicalTrials.gov records for LGD2226 and LGD-2226.
ClinicalTrials.gov lists no study under LGD2226 or LGD-2226. This registry result does not cover unregistered, differently named, or non-U.S. studies. The cited human and regional literature likewise includes no administered-human program.
Read the original sourceStudies and sources
PubChem · LGD-2226 identity
Official chemical identity record
National Center for Biotechnology Information. PubChem CID 11560224.
The record identifies LGD-2226 with formula C14H9F9N2O, molecular weight 392.22 g/mol, CAS 328947-93-9, and UNII RI376RM5MT.
- Study design
- Chemical database record
Identity is not approval or product authentication.
Read the original sourceMiner et al. · rodent efficacy program
Preclinical cell and animal study
Miner JN, Chang W, Chapman MS, Finn PD, Hong MH, López FJ, Marschke KB, Rosen J, Schrader W, Turner R, van Oeveren A, Viveros H, Zhi L, Negro-Vilar A. Endocrinology. 2007;148(1):363-373. DOI 10.1210/en.2006-0793.
LGD-2226 acted as a selective, nonaromatizable androgen-receptor agonist in cell panels and produced muscle, bone, bone-strength, and sexual-behavior effects in androgen- or estrogen-deficient rodent models with less prostate stimulation than testosterone under tested conditions.
- Participants / model
- Cell systems and androgen- or estrogen-deficient rodent models
- Treatment
- Oral LGD-2226 with vehicle and androgen comparators
- Follow-up
- Study-specific short and multi-month rodent experiments
- Study design
- Controlled preclinical pharmacology program
- Funding
- Ligand Pharmaceuticals-associated study
The paper reports rodent surrogate and behavior outcomes; it includes no human strength, fracture, sexual-function, or safety data.
Read the original sourceWang et al., human AR receptor crystal, 2006
Primary preclinical study
Wang F, Liu XQ, Li H, Liang KN, Miner JN, Hong M, Kallel EA, van Oeveren A, Zhi L, Jiang T. Structure of the ligand-binding domain (LBD) of human androgen receptor in complex with a selective modulator LGD2226. Acta crystallographica. Section F, Structural biology and crystallization communications. 2006. DOI 10.1107/s1744309106039340.
The 2.1-angstrom structure binds LGD2226 to isolated human AR ligand-binding domain, with contacts around Gln711 and Arg752. A human protein experiment is not an administered-human trial. The structure shows target binding; it cannot predict whole-body endocrine selectivity or clinical safety.
- Participants / model
- Purified human androgen-receptor ligand-binding domain
- Treatment
- LGD-2226 complex
- Study design
- X-ray crystallography
- Funding
- Industry and structural-biology collaboration
ClinicalTrials.gov · no LGD-2226 study listed
Clinical trial registry
ClinicalTrials.gov records for LGD-2226 and its cited aliases.
ClinicalTrials.gov lists no study under LGD-2226 or its cited aliases. The cited literature likewise includes no human administration report or human pharmacokinetic dataset.
- Participants / model
- ClinicalTrials.gov records
- Treatment
- LGD-2226
FDA · SARM class warning
FDA safety communication
U.S. Food and Drug Administration, updated December 2025.
FDA states that marketed SARM bodybuilding products are unapproved drugs and describes serious cardiovascular, hepatic, reproductive, sexual, and testicular class concerns.
- Participants / model
- Consumers of marketed SARM products
- Treatment
- SARM class
- Study design
- Agency class-risk communication
- Funding
- U.S. FDA
The communication does not provide LGD-2226-specific incidence or prove a particular product's contents.
Read the original sourceWADA 2026 · SARM class applies
Official anti-doping standard
World Anti-Doping Agency. The 2026 Prohibited List, effective 1 January 2026.
Section S1.2 prohibits selective androgen-receptor modulators at all times using an including-but-not-limited-to formulation. LGD-2226 is not named individually in the list.
- Participants / model
- Athletes subject to the World Anti-Doping Code
- Follow-up
- Calendar year 2026
- Study design
- Anti-doping prohibited list
- Funding
- World Anti-Doping Agency
The class assignment follows LGD-2226's primary pharmacology; the list itself does not name it.
Read the original sourceChinese and Russian records · no additional outcome study
Literature and registry records
Chinese and Russian literature and registry records for LGD-2226.
The cited Chinese record is an androgen-receptor crystal-structure paper and reports no administered-subject outcome. The cited Russian records are analytical mentions, reviews, and catalogs without an additional efficacy or safety study.
- Participants / model
- Chinese- and Russian-language records
van Oeveren et al., discovery chemistry, 2006
Primary preclinical study
van Oeveren A, Motamedi M, Mani NS, Marschke KB, López FJ, Schrader WT, Negro-Vilar A, Zhi L. Discovery of 6-N,N-bis(2,2,2-trifluoroethyl)amino- 4-trifluoromethylquinolin-2(1H)-one as a novel selective androgen receptor modulator. Journal of medicinal chemistry. 2006. DOI 10.1021/jm060792t.
The originator paper, DOI 10.1021/jm060792t, identifies orally active tissue-selective 6-dialkylamino quinolinones. Vendor summaries assign compound 4m binding and potency values, but the abstract does not report those exact values, so they are not used here. The medicinal-chemistry series establishes a molecule-development program, not human dosing or selectivity.
Read the original sourceMiner et al., muscle/bone/sexual behavior, 2007
Primary preclinical study
Miner JN, Chang W, Chapman MS, Finn PD, Hong MH, López FJ, Marschke KB, Rosen J, Schrader W, Turner R, van Oeveren A, Viveros H, Zhi L, Negro-Vilar A. Endocrinology. 2007;148(1):363-373. DOI 10.1210/en.2006-0793.
Two-week castrated-rat assays used eight animals per group. Levator-ani mass reached sham values near 3 mg/kg/day; prostate restoration required roughly 100 mg/kg/day. LH suppression differed from testosterone but was not absent. Bone experiments ran for six or sixteen weeks and included mechanical strength. In the eight-week sexual-behavior study, mounts, intromissions, and ejaculation improved versus vehicle, but every group received estradiol implants. Most authors were Ligand employees, and no human outcomes were measured.
Duplicate record for Miner et al. 2007; it is not independent evidence.
Read the original sourceRosen and colleagues, early LGD2226 bone program, 2005
Primary preclinical study
Rosen J, Negro-Vilar A. Novel, non-steroidal, selective androgen receptor modulators (SARMs) with anabolic activity in bone and muscle and improved safety profile. Journal of musculoskeletal & neuronal interactions. 2002. PMID 15758439.
Skeletally mature orchiectomized male rats underwent four months of exposure. The paper reports suppression of increased bone turnover, maintained density, cortical bone formation and improved mechanical quality, together with levator-ani activity. The abstract does not expose complete group denominators, allocation or numerical effect estimates. The same originator program and duration overlap with later work; without cohort identifiers it should not be counted as wholly independent replication.
Abstract and bibliographic record only.
Read the original sourceThevis et al., anti-doping detection, 2007
Analytical identity or detection study
Thevis M, Kohler M, Maurer J, Schlörer N, Kamber M, Schänzer W. Screening for 2-quinolinone-derived selective androgen receptor agonists in doping control analysis. Rapid communications in mass spectrometry : RCM. 2007. DOI 10.1002/rcm.3247.
Four quinolinone SARMs, including LGD2226, were synthesized and characterized for urine screening. Detection limits were 0.01 to 0.2 ng/mL and recovery was 81 to 98%. The work validated an analytical method and did not administer LGD-2226 as a treatment.
Abstract only.
Read the original sourceLigand SEC development record
Official scientific or regulatory record
Ligand SEC development record. https://www.sec.gov/Archives/edgar/data/886163/000088616303000010/ligand200210k.htm
The 2002 annual report lists LGD2226/backups as IND-track with TAP rights for hormone-related indications. A company development plan is not evidence that a human trial started or completed. Later secondary accounts report discontinuation, but the cited primary records do not explain why.
Company regulatory filing.
Read the original sourceClinicalTrials.gov · no exact-name study
Clinical trial registry
ClinicalTrials.gov records for LGD2226 and LGD-2226.
ClinicalTrials.gov lists no study under LGD2226 or LGD-2226. This registry result does not cover unregistered, differently named, or non-U.S. studies. The cited human and regional literature likewise includes no administered-human program.
Read the original sourceWhy is LGD-2226 in D tier?
D: rodent muscle, bone-strength and sexual-behavior results, with no human trial or pharmacokinetic study in the cited evidence. Every sexual-behavior group received estradiol, and animal tissue selectivity does not establish endocrine safety in people.