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Related Concept Videos

Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

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Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
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Introduction to Nuclear Reprogramming01:14

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Nuclear reprogramming is the process of switching gene expression of one cell type to that of another cell type, usually from a differentiated cell state to an undifferentiated cell state. Differentiation occurs during processes such as development and morphogenesis, tissue regeneration, and malignancy. Cells can also be artificially induced to reprogram their gene expression by techniques such as nuclear transfer, induced pluripotency, and cell fusion. Such techniques have many applications in...
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Signal Transduction: Overview01:26

Signal Transduction: Overview

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Cells respond to many types of information, often through receptor proteins positioned on the membrane. They respond to chemical signals, such as hormones, neurotransmitters, and other signaling molecules, initiating a series of molecular reactions to produce an appropriate response. This is called signal transduction. Cells also coordinate different responses elicited by the same signaling molecule via mediators, allowing molecular cross-talk.
Typically, signal transduction involves three...
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Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

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Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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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.
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Regulation of Nuclear Protein Sorting01:45

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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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Updated: Feb 28, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Nuclear Receptor-Targeted Therapies: Reprogramming Metabolism with TRβ, ERRα, and LXR Modulators.

Carmen Di Giovanni1, Antonio Lavecchia1

  • 1"Drug Discovery" Laboratory, Department of Pharmacy, University of Naples Federico II, I-80131 Naples, Italy.

Biomolecules
|February 27, 2026
PubMed
Summary
This summary is machine-generated.

Targeting nuclear receptors like TRβ, ERRα, and LXR offers a new precision medicine approach for metabolic disorders. Modulators show promise in treating fatty liver disease, obesity, and dyslipidemia, restoring metabolic health.

Keywords:
estrogen-related receptor αliver X receptormetabolic disordersmitochondrial biogenesisnon-alcoholic fatty liver diseasenuclear receptorssmall-molecule modulatorstargeted therapythyroid hormone receptor β

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Area of Science:

  • Pharmacology
  • Endocrinology
  • Hepatology

Background:

  • Metabolic disorders, including MAFLD, obesity, and dyslipidemia, represent a growing global health challenge requiring novel pharmacotherapies.
  • Nuclear receptor (NR) modulation is a key strategy for restoring metabolic homeostasis.
  • TRβ, ERRα, and LXR are pivotal NRs for metabolic regulation with significant therapeutic potential.

Purpose of the Study:

  • To review recent advances in small-molecule modulators targeting TRβ, ERRα, and LXR.
  • To discuss the translational potential of these modulators for metabolic diseases.
  • To highlight the role of NR modulation in precision medicine for metabolic disorders.

Main Methods:

  • Review of recent scientific literature on TRβ, ERRα, and LXR modulators.
  • Analysis of preclinical and clinical data for small-molecule drugs targeting these NRs.
  • Examination of drug design strategies for selective and potent NR modulation.

Main Results:

  • TRβ agonists (resmetirom, VK2809) show efficacy in treating MASH, reducing liver fat and fibrosis.
  • Next-generation TRβ modulators (e.g., TG68) improve tissue specificity and potency.
  • ERRα modulators demonstrate potential in preclinical obesity models for insulin resistance and lipid oxidation.
  • LXR drug design focuses on selective agonists to achieve atheroprotective benefits while minimizing triglyceride synthesis issues.

Conclusions:

  • TRβ, ERRα, and LXR modulators represent a promising new frontier in precision medicine.
  • These NRs offer powerful strategies to reprogram dysregulated metabolic pathways.
  • Targeted NR modulation holds substantial promise for the effective treatment of metabolic diseases.