Nuclear Hormone Receptor 4A/NR4A Inhibitor

Celastrol (Tripterine;Tripterin) is a proteasome inhibitor which potently and preferentially inhibits the chymotrypsin-like activity of a purified 20S proteasome with IC₅₀ of 2.5 μM. In addition, Celastrol is also an antibiotic with potent antimicrobial activity against standard and clinical methicillin-resistant Staphylococcus aureus (MRSA) strains, inducing oxidative stress and inhibiting DNA synthesis by binding to P5CDH.

Glycerol kinase, microorganism (GyK) acts as a NR4A1 inhibitor with enzymatic activity. It directly binds to and inhibits the transcription factor NR4A1, thereby negatively regulating hepatic gluconeogenesis and reducing blood glucose levels. Glycerol kinase, microorganism positively regulates UCP1 expression via partial dependence on the β-adrenergic receptor-cAMP-CREB pathway, promotes browning of white adipose tissue and thermogenesis, and further modulates intracellular fatty acid composition and energy metabolism. In diabetic mouse models, overexpression of Glycerol kinase effectively antagonizes NR4A1-induced hyperglycemia, demonstrating potential for improving glucose homeostasis. Glycerol kinase, microorganism can be used for studies on diabetes and obesity.

Nurr1/RXR dual agonist 1 is a dual activator of Nurr1 (EC₅₀ = 2.6 µM) and RXR with Ks of 0.6 and 1.1 µM, respectively. Nurr1/RXR dual agonist 1 exclusively activates the heterodimer response element DR5 by selectively destabilizing the Nurr1 homodimer and stabilizing the Nurr1:RXR heterodimer. Nurr1/RXR dual agonist 1 enhances expression of a specific subset of neuroprotective Nurr1 target genes while avoiding induction of genes associated with potential off-target effects in neuronal cells. Nurr1/RXR dual agonist 1 can be used for neurodegenerative diseases research.