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Updated: Jun 18, 2026

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay
Published on: December 19, 2018
Amino-Acid-Derived Androgen Receptor Modulators
Julius Semenya1, Elias Picazo1
1Department of Chemistry, Loker Hydrocarbon Research Institute, University of Southern California, 837 Bloom Walk, Los Angeles, California 90089-1661, United States.
None:
Amino-acid-derived arylpropionamide androgen receptor (AR) modulators, termed EPic AR modulators, have been developed through an efficient 2-3 step synthesis from commercially available enantioenriched amino acid starting materials. This modular route delivers gram-scale quantities of the targets in excellent yield and with high enantiomeric excess (>99% ee), overcoming limitations in the enantioselective preparation of selective androgen receptor modulators (SARMs) and antiandrogens (AAs) while unlocking the previously invariant α-amido heteroatom for structural diversification. Binding assays reveal strong AR affinity for several analogs. Initial validation through cellular reporter assays demonstrates tunable antagonism, with select compounds exhibiting a distinctive biphasic profile: low-efficacy partial agonism at low concentrations that transitions to antagonism at higher doses. These results establish a powerful, operationally simple platform for the rapid generation of stereochemically defined AR modulators, offering new opportunities for next-generation therapeutics in muscle-wasting disorders, oncology supportive care, and androgen-related diseases.
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