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Updated: Jan 31, 2026

Incorporation of a Survivable Liver Biopsy Procedure in Mice to Assess Non-alcoholic Steatohepatitis NASH Resolution
Published on: April 16, 2019
The metabolic dysfunction-associated steatohepatitis (MASH) drug resmetirom exhibits broad nuclear receptor activity
Annette Kärcher1, Laura Isigkeit2,3, Nils Christiaan Bandomir1
1Goethe University Frankfurt, Institute of Pharmaceutical Chemistry, Max-Von-Laue-Str. 9, 60438, Frankfurt, Germany.
Abstract:
In 2024, the FDA granted approval for resmetirom, a selective but moderately potent agonist of the thyroid hormone receptor (THR) β, marking the first drug for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) in the US. Given the absence of selectivity data, we conducted a comprehensive screening against other nuclear receptors implicated in metabolic regulation, in addition to THRβ. Reporter gene assays revealed that resmetirom also binds several off-target nuclear receptors, including constitutive androstane receptor (CAR), retinoic acid receptor-related orphan receptors (RORs), and hepatocyte nuclear factor 4α (HNF4α). However, subsequent in vitro experiments, designed to better recapitulate physiological conditions, showed that THRβ modulation is functionally dominant. These preliminary findings suggest that pharmacotherapeutic efficacy of resmetirom remains intact despite the identified off-target effects, supporting its clinical application in the treatment of MASH.
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