Orphan nuclear receptors: structural mechanisms, ligand discovery, and therapeutic potential - PubMed
3 hours ago
- #nuclear receptors
- #therapeutic target
- #ligand discovery
- Orphan nuclear receptors (ONRs) are nuclear receptor superfamily members lacking known high-affinity endogenous ligands.
- ONRs play crucial roles in metabolism, development, neural function, and tumorigenesis, linked to diseases like metabolic disorders, cancers, and neurological conditions.
- Structural biology has revealed ligand-binding domain features, identifying ligands such as lipids, heme, and phospholipids for receptors like ROR, HNF-4, and REV-ERB.
- Ligand discovery strategies include endogenous ligand co-purification, high-throughput screening, structural approaches, and virtual screening with molecular dynamics.
- Challenges in ONR research include identifying endogenous ligands, context-dependent regulation, and achieving subtype selectivity for therapeutic development.