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Updated: Aug 11, 2026
12:36
Murine Precision-Cut Liver Slices as an Ex Vivo Model of Liver Biology
Published on: March 14, 2020
Pulsatile FXR activation for liver diseases
Pingxin Sun1, Ke Feng1, Wenlin Li2
1Department of Cell Biology, Naval Medical University, Shanghai 200433, China.
Cell Metabolism
|August 4, 2026
Summary
Sustained receptor activation is not always best for drug development. A new farnesoid X receptor agonist, linafexor, shows pulsatile activation improves metabolic therapeutics
Area of Science:
- Pharmacology
- Metabolic Diseases
- Drug Development
Background:
- Sustained receptor activation is a common strategy in developing new drugs.
- This approach can lead to reduced receptor responsiveness and unintended transcriptional effects.
Purpose of the Study:
- To investigate the therapeutic potential of pulsatile receptor activation.
- To evaluate a novel farnesoid X receptor (FXR) agonist, linafexor, designed for rapid clearance and transient signaling.
Main Methods:
- Development and testing of linafexor, a FXR agonist.
- Assessment of linafexor's pharmacokinetic profile and its impact on receptor activation patterns.
- Evaluation of transcriptional changes and therapeutic outcomes in preclinical models.
Main Results:
- Linafexor demonstrated rapid clearance and induced pulsatile, rather than sustained, FXR activation.
- Pulsatile activation preserved receptor responsiveness and minimized off-target transcriptional disruption.
- This approach improved efficacy and safety profiles compared to sustained activation strategies.
Conclusions:
- Temporal alignment, specifically pulsatile activation, is a viable and potentially superior design principle for metabolic therapeutics.
- Linafexor exemplifies a new class of drugs that leverage transient signaling for enhanced therapeutic outcomes.
- This study challenges the conventional focus on sustained receptor engagement in drug design.
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