Liver X Receptor Related Drug Discovery Products

The Liver X Receptor (LXR) family constitutes a duality of nuclear receptors, LXRα (NR1H3) and LXRβ (NR1H2), which exhibit a high degree of homology and collectively preside over an array of physiological phenomena, including lipid metabolism, cholesterol equilibration, and inflammatory response modulation. As detectors of oxysterols, cholesterol derivatives, LXR receptors permeate a wide range of tissues, albeit LXRα displays a predilection for the liver, intestine, adipose tissue, and macrophages, while LXRβ evinces a more pervasive distribution. The complexities inherent to LXR biology have captivated scientific inquiry, inspiring the deployment of sophisticated methodologies and resources to scrutinize the potential of LXRs as therapeutic foci, whilst circumventing an emphasis on pathological manifestations and pharmacological intercessions.

Fig.1 LXRs may be linked to a variety of pathological disorders. (Komati, 2017)

As a pioneer in the field of drug discovery and development, Creative Biolabs can offer high-quality liver X receptor tools to our customers:

• Liver X Receptor Assays
• Membrane Protein Tools

Overview of Liver X Receptor

The Liver X Receptor family, an assemblage of two discrete yet functionally interconnected subtypes, LXRα (NR1H3) and LXRβ (NR1H2), occupies a cardinal position in the orchestration of lipid metabolism, cholesterol equilibrium, and immunological processes. Both LXR subtypes are subject to activation by oxysterols, derivatives of cholesterol metabolism. Subsequent to ligand engagement, LXRs establish heterodimeric complexes with Retinoid X Receptors (RXRs) and associate with LXR response elements (LXREs) situated within the promoter domains of cognate genes, thereby exerting control over their transcriptional activity. In the ensuing discourse, a comprehensive elucidation of the LXR subtypes and their multifarious roles is proffered.

• LXRα (NR1H3):

The LXRα subtype conspicuously materializes in tissues encompassing the liver, intestine, adipose tissue, and macrophages, where it assumes a paramount function in the preservation of lipid and cholesterol equilibrium. LXRα presides over the transcriptional modulation of a plethora of genes entwined in cholesterol efflux, bile acid genesis, fatty acid synthesis, and lipogenesis. Moreover, LXRα has been implicated in the adjustment of immune reactions, particularly through the mitigation of inflammatory signaling trajectories within macrophages.

• LXRβ (NR1H2):

LXRβ, in contrast to LXRα, is characterized by a more ubiquitous expression pattern, albeit with a predilection for tissues such as brain, lung, kidney, and spleen. LXRβ, similar to its counterpart, is a key regulator of lipid and cholesterol homeostasis, eliciting its effects through the transcriptional control of genes involved in cholesterol efflux, bile acid synthesis, and fatty acid synthesis. Additionally, LXRβ is implicated in the modulation of immune responses, particularly in the regulation of anti-inflammatory pathways.

Liver X Receptor Drug Discovery

The quest for synthetic compounds that can selectively modulate LXR activity has incited a fertile area of investigation, with a focus on agonists and partial agonists that may bolster the beneficial aspects of LXR activation while mitigating potential adverse effects. Pioneering endeavors in medicinal chemistry aim to devise novel LXR ligands with enhanced in vivo biodistribution, tissue selectivity, and structure-activity relationships, all of which are essential for harnessing the potential of LXRs in modulating physiological processes.

Fig.2 Pathways of LXR signaling in cholesterol and fatty acid metabolism. (Wang, 2018)

References

1. Komati, R.; et al. Ligands of therapeutic utility for the liver X receptors. Molecules. 2017, 22(1): 88.
2. Wang, B.; Tontonoz, P. Liver X receptors in lipid signaling and membrane homeostasis. Nature Reviews Endocrinology. 2018, 15: 452-463.