LGD-2226

LGD-2226 (Selective Androgen Receptor Modulator)

LGD-2226 is a synthetic, nonsteroidal small-molecule Selective Androgen Receptor Modulator (Selective Modulator) originally developed by Ligand Pharmaceuticals in collaboration with researchers at the University of Tennessee. Belonging to the 6-alkylamino-2-quinolinone structural class, it is recognized for its high-affinity binding and significant selectivity profile. LGD-2226 acts as a selective agonist, inducing a distinct ligand-binding domain conformation upon binding to the androgen receptor, which differs from that of steroidal androgens like testosterone.

Technical Specifications

Pharmacology & Research Context

LGD-2226 is characterized by its high binding affinity to the androgen receptor and significant selectivity over other steroid hormone receptors (GR, PR, MR, and ER). The presence of nine fluorine atoms distributed across three trifluoromethyl/trifluoroethyl groups provides substantial electron-withdrawing character, which influences its lipophilicity, metabolic stability, and receptor binding kinetics.

• Receptor Affinity: Reported $K_i$ of approximately 1 nM.

• Selectivity: $> 1,000$-fold selectivity over glucocorticoid, progesterone, mineralocorticoid, and estrogen receptors.

• Mechanism: Induces a unique androgen receptor protein-protein interaction pattern, distinct from steroidal ligands, leading to differential transcriptional output in cell-based reporter models.

Research Applications

LGD-2226 serves as a high-affinity ligand and reference standard in androgen receptor pharmacological research and analytical method development.

Primary fields of laboratory investigation include:

• Receptor Pharmacology: Androgen receptor binding and competition assays.

• Structure-Activity Relationship (SAR): Comparative analysis within the 2-quinolinone structural class.

• Selectivity Profiling: Evaluating nuclear receptor selectivity across the steroid hormone receptor family.

• Analytical Method Development: Use as a reference standard for LC-MS/MS panels, including anti-doping analytical protocols.

• Conformation Studies: Investigating ligand-binding domain conformation and its downstream transcriptional effects.

Storage & Handling Guidelines

To maintain the structural stability and purity of the compound, the following protocols are recommended:

• Long-Term Storage: Store powder at -20 °C.

• Short-Term Storage: Room temperature is acceptable for active research use.

• Environmental Control: Protect from direct light and keep in a tightly sealed container.

• Moisture Protection: Use desiccant for powder storage to prevent degradation.

• Handling: Adhere to appropriate laboratory handling procedures and wear required Personal Protective Equipment (PPE).

Regulatory & Research Use Disclaimer

Research Use Only Disclaimer: This product is developed and distributed strictly as a Research Use Only (RUO) laboratory reference chemical intended exclusively for non-clinical analytical and scientific investigation. It is not intended for human consumption, clinical use, veterinary use, therapeutic application, or diagnostic use. LGD-2226 is included on the World Anti-Doping Agency (WADA) Prohibited List under the anabolic agents category. All handling, preparation, and experimental use must comply with applicable federal, state, and local laws, as well as institutional laboratory safety standards. Kimera Chems supplies this reagent exclusively to qualified researchers and scientific institutions.