LGD-2226

Overview

LGD-2226 is a nonsteroidal selective androgen receptor modulator (SARM) — a bicyclic 6-anilino-quinolinone small molecule (PubChem CID 11560224, CAS 328947-93-9). It is not a peptide. It was discovered by Ligand Pharmaceuticals (van Oeveren et al.), with TAP Pharmaceutical Products cited as a co-development partner, as a candidate for muscle wasting and osteoporosis.

The entire evidence base for LGD-2226 is preclinical — animal and in-vitro only. It was never approved as a medicine, and on the available record it most likely never completed a Phase 1 human trial. A 2000-era BioWorld headline signaled development intent, but no verifiable IND filing or ClinicalTrials.gov/NCT record exists, and reviews classify the compound as preclinical. It later re-surfaced (~2020) as an illicit "designer" SARM in the grey market.

Chemistry and structure

Mechanism of action

• Binds the androgen receptor (AR) as a high-affinity, high-potency nonsteroidal agonist. Reported EC50 ~0.2 nM in cell-based AR transactivation assays and Ki ~1–1.5 nM at the human AR; it is a nonsteroidal, non-aromatizable ligand. [In vitro]
• >1000-fold selectivity for AR over other nuclear/steroid receptors. Virtually no affinity for glucocorticoid (GR), progesterone (PR), mineralocorticoid (MR), or estrogen (ER) receptors. [In vitro]
• Induces a unique AR ligand-binding-domain conformation. AR bound to LGD2226 shows a distinct pattern of protein–protein (coregulator) interactions versus testosterone, proposed to underlie its tissue-selective (SARM) behavior — anabolic in muscle/bone, less androgenic in prostate. [In vitro]
• Tissue-selective anabolic action in vivo. In castrated rodents, it was anabolic on the levator ani muscle and on bone mass/strength, maintained male reproductive behavior, and had reduced effect on prostate weight with less suppression of luteinizing hormone than testosterone. [Animal]

Research and evidence

The published record for LGD-2226 is preclinical only. The key primary study is Miner JN et al., Endocrinology 2007;148(1):363–373 (PMID 17023534), which characterized an orally active SARM efficacious on bone, muscle, and sex function with reduced impact on prostate in rodent models.

• Model: Castrated rodents and cell-based assays. No human trials.
• Phase: Preclinical. Human-trial status is unverified — most likely never completed Phase 1. No verifiable IND filing or NCT record exists; a BioWorld headline (~2000) signaled development intent only.
• Human efficacy: Never tested in humans (muscle wasting or osteoporosis). No human efficacy data exist.

Evidence level: Preclinical — animal/in-vitro only.

Status and regulation

LGD-2226 has never been an approved medicine in any jurisdiction. It is a preclinical research compound. The developer was Ligand Pharmaceuticals (discovery, van Oeveren et al.), with TAP Pharmaceutical Products cited as a co-development partner; the exact nature and current status of that partnership on this specific compound is not established in the sources.

It is prohibited in sport under WADA class S1.2 (Other Anabolic Agents — SARMs), and SARMs have been WADA-listed since 2008. Anti-doping status is separate from a compound's legal status, which is not assessed here.

Safety

• No human safety data. LGD-2226 has no published human efficacy or safety data; all evidence is animal/in-vitro. Any human use is off-label, non-clinical exposure to an unapproved research chemical with an unknown human risk profile. [Hypothesis]
• SARM-class hepatotoxicity / drug-induced liver injury (DILI). The FDA has warned that SARMs as a class are associated with serious harms including liver injury and acute liver failure; multiple published case reports document DILI from other SARMs (e.g., LGD-4033, RAD140). No LGD-2226-specific human liver data exist, but the class signal applies. [Human]
• Testosterone / HPTA suppression. As an AR agonist, SARMs of this class suppress the hypothalamic–pituitary–testicular axis (endogenous testosterone), with reported effects including testicular shrinkage and infertility for the class. Not specifically studied in humans for LGD-2226. [Hypothesis]
• Class cardiovascular and other harms. FDA-cited SARM-class risks include increased risk of heart attack and stroke; psychosis/hallucinations and sexual dysfunction have also been reported for the class. Compound-specific human data for LGD-2226 do not exist. [Human]
• Prohibited in sport. Banned under WADA class S1.2 (Other Anabolic Agents — SARMs); WADA-listed since 2008. [Human]

Product contamination / mislabeling reality. Products sold as "SARMs" are frequently mislabeled. Van Wagoner et al., JAMA 2017;318(20):2004–2010 (PMID 29183075) found that only 52% of tested "SARM" products contained the labeled SARM, 39% contained a different unapproved drug, and 9% contained no active compound at all. A label is not a reliable statement of contents. LGD-2226 itself has been encountered as an illicit "designer" SARM (~2020). [Human]

Legal status

Legal status is not assessed on this page and varies by jurisdiction. LGD-2226 is an unapproved research chemical, not an approved medicine, and is not authorized for human consumption. Its status in sport (prohibited under WADA S1.2) is separate from — and does not determine — its legal status in any country. This is not legal advice (dated 2026-07-10).

How it compares

LGD-2226 sits in the same nonsteroidal SARM research family as compounds such as ligandrol (LGD-4033) and testolone (RAD140), which — unlike LGD-2226 — have some human clinical data. LGD-2226 is further back on the development path: it remained preclinical and most likely never completed a Phase 1 trial.

Common misconceptions

• "It's a peptide." No. LGD-2226 is a small-molecule nonsteroidal SARM, not a peptide.
• "It's a proven muscle/bone drug in humans." No. All evidence is preclinical (rodent/in-vitro). There is no human efficacy or safety data.
• "It reached clinical trials." Unverified and unlikely. No IND filing or NCT record can be confirmed; reviews classify it as preclinical.
• "It's a safer or legal alternative to steroids." No. It is unapproved, carries class-level FDA safety warnings, has no human safety data, and is prohibited in sport under WADA.