LGD-2226 Research Standard

LGD-2226 (CAS 328947-93-9) is a nonsteroidal, nonaromatizable quinolinone-class selective androgen receptor modulator, supplied as a reference standard for androgen receptor pharmacology and analytical method development. It came out of a medicinal-chemistry programme on 6-dialkylamino-4-trifluoromethylquinolin-2(1H)-ones, and it is a useful comparator precisely because its scaffold is unrelated to both the steroid nucleus and the arylpropionamide SARMs.^[1]

Mechanism of Action & Research Context

The molecular target is the androgen receptor (AR, NR3C4), a ligand-activated nuclear hormone receptor acting as a transcription factor.

• High selectivity for AR. LGD-2226 is a highly selective AR ligand, exhibiting virtually no affinity for the other intracellular receptors — which makes it a clean tool where a steroidal androgen would engage several.^[2]

• A distinct receptor conformation. This is the mechanistically interesting part. AR bound to LGD-2226 shows a different pattern of protein-protein interactions than AR bound to testosterone or to the steroidal androgen fluoxymesterone, indicating that the ligand alters the conformation of the ligand-binding domain. Differential coregulator recruitment following that conformational change is the leading account of how one receptor produces tissue-dependent outputs.^[2]

• Nonaromatizable. It cannot be converted to an estrogenic ligand, so effects observed with it are attributable to AR engagement rather than to downstream estrogen receptor signalling — a confound that complicates work with aromatizable steroids.^[2]

• Genomic and non-genomic arms. Across the class, nonsteroidal SARMs and endogenous androgens engage AR through distinct genomic and non-genomic routes and assemble different AR/cofactor complexes at androgen-responsive enhancers.^[4]

• Cell-based activity. LGD-2226 is fully active in cell-based models of bone and muscle.^[2]

Research Applications

Primary fields of in vitro and preclinical laboratory investigation include:

• Competitive AR binding assays with nuclear receptor counter-screens.^[1,2]

• Coregulator interaction profiling comparing ligand-specific protein-protein interaction patterns against steroidal androgens.^[2,4]

• AR transactivation reporter assays in transfected cell lines.^[1]

• Structure-activity relationship work across the quinolinone scaffold.^[1]

• Analytical and forensic method development. LGD-2226 is among the SARMs covered by established chromatography-mass spectrometry screening methods, making it a standard reference analyte.^[3]

Analytical Documentation

Purity and identity vary by manufacturing lot. Kimera Chems does not publish a single fixed purity figure for this item; refer to the batch-specific Certificate of Analysis (COA) issued for the lot received, which reflects third-party analytical testing for that lot.

Storage & Handling

Store at controlled room temperature. Keep tightly closed. Liquid formats: do not refrigerate or freeze. Cold storage may cause the solution to cloud or precipitate. If this occurs, return to room temperature and mix until clear.

Storage guidance is a house recommendation. Analytical documentation is per-lot release testing.