Pharmacological Research - Natural Products, Journal Year: 2024, Volume and Issue: unknown, P. 100116 - 100116
Published: Oct. 1, 2024
Language: Английский
Communications Chemistry, Journal Year: 2025, Volume and Issue: 8(1)
Published: Feb. 3, 2025
Abstract The nine human NR3 nuclear receptors translate steroid hormone signals in transcriptomic responses and operate multiple highly important processes ranging from development over reproductive tissue function to inflammatory metabolic homeostasis. Although several ligands such as glucocorticoids are invaluable drugs, this family is only partially explored, for example, autoimmune diseases neurodegeneration, but may hold therapeutic potential new areas. Here we report a chemogenomics (CG) library reveal elusive effects of receptor modulation phenotypic settings. 34 annotated chemically diverse covering all were selected considering complementary modes action activity, selectivity lack toxicity. Endoplasmic reticulum stress resolving N3 CG subsets proof-of-concept application validate suitability the set connect outcomes with targets explore translational perspective.
Language: Английский
Citations
0
ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: 16(4), P. 575 - 582
Published: March 20, 2025
The phospholipid sensing transcription factor liver receptor homologue 1 (LRH-1) participates in the transcriptional regulation of metabolic balance and inflammation liver, pancreas, other tissues. It is an emerging target for dysfunction, fatty disease, cancer, but LRH-1 modulators are rare lack drug-like properties. We discovered new ligands with improved physicochemical features a fragment-based approach optimized venlafaxine-related lead activation. Despite strict structure-activity relationship, systematic structural variation resulted agonist scaffold strong activation efficacy, validated direct cellular engagement, anti-inflammatory ER-stress-resolving properties functional settings.
Language: Английский
Citations
0
Food Research International, Journal Year: 2025, Volume and Issue: unknown, P. 116308 - 116308
Published: March 1, 2025
Language: Английский
Citations
0
Published: March 25, 2025
Metabolic dysfunction-associated steatotic liver disease (MASLD) is rapidly emerging as a global health crisis, affecting over 30% of the population and demanding urgent attention. This redefined condition, previously known non-alcoholic fatty (NAFLD), reflects deeper understanding intricate interplay between metabolic dysfunction health. At heart MASLD lies troubling accumulation triglycerides (TGs) in hepatocytes, which precipitates insulin resistance oxidative stress, ultimately leading to more severe forms like steatohepatitis (MASH). Excitingly, recent research has spotlighted farnesoid X receptor (FXR) groundbreaking therapeutic target. FXR not only regulates lipid metabolism but also combats inflammation resistance, making it potential game-changer fight against MASLD. With one FDA-approved drug, resmetirom, currently available, exploration agonists opens new avenues for innovative treatments that could revolutionize patient care. By harnessing power restore balance integrating advanced strategies lipidomics acid profiling, we stand on brink transforming how approach its associated complications, paving way healthier future. review delves into promising role combating implications related disorders, emphasizing urgency detect manage this burgeoning epidemic.
Language: Английский
Citations
0
Metabolism, Journal Year: 2024, Volume and Issue: unknown, P. 156128 - 156128
Published: Dec. 1, 2024
Language: Английский
Citations
1
Pharmacological Research - Natural Products, Journal Year: 2024, Volume and Issue: unknown, P. 100116 - 100116
Published: Oct. 1, 2024
Language: Английский
Citations
0