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.
References
- van Oeveren A, Motamedi M, Mani NS, et al. Discovery of 6-N,N-bis(2,2,2-trifluoroethyl)amino-4-trifluoromethylquinolin-2(1H)-one as a novel selective androgen receptor modulator. J Med Chem. 2006;49(21):6143–6146. doi:10.1021/jm060792t
- Miner JN, Chang W, Chapman MS, et al. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology. 2007;148(1):363–373. doi:10.1210/en.2006-0793
- Thevis M, Schänzer W. Detection of SARMs in doping control analysis. Mol Cell Endocrinol. 2017;464:34–45. doi:10.1016/j.mce.2017.01.040
- Narayanan R, Coss CC, Yepuru M, et al. Steroidal androgens and nonsteroidal, tissue-selective androgen receptor modulator, S-22, regulate androgen receptor function through distinct genomic and nongenomic signaling pathways. Mol Endocrinol. 2008;22(11):2448–2465. doi:10.1210/me.2008-0160
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.
