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Updated: May 3, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Discovery and SAR study of hydroxyacetophenone derivatives as potent, non-steroidal farnesoid X receptor (FXR)
Peng Liu1, Xing Xu2, Lili Chen2
1Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
Abstract:
Compound 1 (IC50=35.2 ± 7.2 μM), a moderate FXR antagonist was discovered via high-throughput screening. Structure-activity relationship studies indicated that the shape and the lipophilicity of the substituents of the aromatic ring affect the activity dramatically, increasing the shape and the lipophilicity of the substituents of the aromatic ring enhances the potency of FXR antagonists. Especially, when the OH at C2 position of the aromatic ring was replaced by the OBn substituent (analog 2b), its activity could be improved to IC50=1.1 ± 0.1μM. Besides, the length of the linker and the tetrazole structure are essential for retaining the activity.
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