Targeting THR-β for MASLD: Mechanisms and Drug Development
Yunlong Hua1, Yang Liu2, Lianjun Xing3
1Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People's Republic of China.
Drug Design, Development and Therapy
|December 1, 2025
Summary
Metabolic dysfunction-associated steatotic liver disease (MASLD) is common, with few treatments. Thyroid hormone receptor beta (THR-β) agonists, like Resmetirom, show promise for MASLD by targeting liver metabolism, but further research is needed.
Area of Science:
- Hepatology
- Endocrinology
- Pharmacology
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease globally, lacking effective therapies.
- Thyroid hormone (TH) and its receptor THR-β are critical regulators of hepatic metabolism, making THR-β a key therapeutic target for MASLD.
Purpose of the Study:
- To review the mechanisms of TH/THR-β in MASLD.
- To summarize recent advances in THR-β-targeted pharmacotherapy for MASLD.
- To discuss the therapeutic potential and challenges of THR-β agonists in MASLD treatment.
Main Methods:
- Literature review of studies on thyroid hormone action in the liver.
- Analysis of preclinical and clinical data for THR-β agonists in MASLD.
- Discussion of disease heterogeneity and drug adverse reactions.
Main Results:
- THR-β agonists demonstrate efficacy in reducing hepatic steatosis, inflammation, and fibrosis in MASLD.
- Resmetirom, a selective THR-β agonist, received FDA approval in 2024.
- Ongoing research into other THR-β agonists shows therapeutic promise.
Conclusions:
- THR-β targeted pharmacotherapy represents a significant advancement in MASLD treatment.
- Further comprehensive assessment of clinical efficacy and safety is crucial.
- Continued research is essential for optimizing drug development and clinical application of THR-β agonists for MASLD.
Related Concept Videos
01:27Transducer Mechanism: Enzyme-Linked Receptors
3.8K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
3.8K
02:57Targeted Cancer Therapies
8.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
8.6K
01:26Targets for Drug Action: Overview
10.0K
Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
10.0K
01:29Therapeutic Drug Monitoring: Affecting Factors
182
Therapeutic Drug Monitoring (TDM) is the clinical practice of measuring specific drug levels in a patient's blood or body tissues to manage and optimize therapy. TDM is crucial for drugs with narrow therapeutic windows, like warfarin and phenytoin, where incorrect doses can lead to treatment failure or severe side effects. This monitoring ensures the dosage administered is within a safe and effective range. The factors affecting therapeutic drug monitoring include:Patient-Specific Factors:a.
182
01:16Therapeutic Drug Monitoring: Overview and Classification
275
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood at designated intervals to ensure the drug concentration stays within a therapeutic range. This monitoring is crucial for optimizing individual dosage regimens, enhancing therapeutic efficacy, and minimizing drug-related toxicity. TDM is vital for drugs with narrow therapeutic windows, significant variability in pharmacokinetics, and a clear correlation between plasma levels and...
275
01:26Therapeutic Drug Monitoring: Drug Analysis Methods
164
Therapeutic Drug Monitoring (TDM) is a clinical practice that measures specific drug levels in a patient's blood or body tissues to tailor drug therapy effectively. This monitoring is critical for managing drugs with narrow therapeutic indices like digoxin and phenytoin, ensuring they are both safe and effective. For instance, monitoring theophylline levels in asthma patients involves precision and sensitivity to adjust doses according to individual responses to therapy, ensuring efficacy and...
164