Unraveling the Molecular Basis for DAF -12 Activation: Diastereoselective Synthesis and SAR Studies of Dafachronic Acid Derivatives

With the aim to better define the biological relevance, endocrine circuitry and molecular mechanism governing the action of DAF-12, we report the diastereoselective synthesis, biological appraisals, and structure-activity relationships of a series of DA derivatives as novel DAF-12 ligands. The results revised in the light of computational analysis have provided further mechanistic insights into the molecular features of the receptor activation and may be useful in designing and identifying species-selective DA-based modulators.