LGD-2226

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

1. 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
2. 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
3. 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
4. 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.

Related Research Compounds

• GSK-2881078
• OTR-AC
• CB-03-01
• MID-35

Research Use Only Disclaimer: This product is labeled and sold "For Research Use Only - NOT FOR HUMAN CONSUMPTION." It is not a drug, dietary supplement, food, cosmetic, or medical device, and it is not approved by the FDA or any other regulator for human or veterinary use. It is supplied to approved account holders as a research chemical for laboratory use and must be handled in accordance with applicable law.