Pulsatile FXR activation for liver diseases.

Sun, Pingxin; Feng, Ke; Li, Wenlin · Cell Metab · 2026

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Abstract

Sustained receptor activation is often prioritized in drug development. Zang and colleagues challenge this paradigm with linafexor, a rapidly cleared farnesoid X receptor agonist that produces pulsatile activation, preserves receptor responsiveness, reduces broad transcriptional disruption, and improves efficacy and safety, highlighting temporal alignment as a design principle for metabolic therapeutics.

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