Nurr1 agonist 29 is a potent, selective nuclear receptor related 1 (Nurr1, NR4A2) agonist with EC50 of 0.11 uM.
Nurr1 agonist 29 displays selectivity over DHODH as well as the Nurr1 related receptors Nur77 and NOR1.
Nurr1 agonist 29 exhibits high-affinity binding to the Nurr1 LBD in ITC (Kd = 0.3 μM) and activates full-length human Nurr1 on the monomer (NBRE, EC50=0.22 μM) and the RXR-heterodimer (DR5, EC50=0.36 μM) response elements.
Nurr1 agonist 29 induces mRNA expression of the Nurr1-regulated genes tyrosine hydroxylase (TH) and vesicular amino acid transporter 2 (VMAT2) in Nurr1-expressing human astrocytes (T98G), demonstrating cellular target engagement.
Nurr1 agonist 29 shows no cytotoxic effects in a multiplex toxicity assay in COS-7 cells.
Nurr1 agonist 29 (5 mg/kg) produced a very favorable pharmacokinetic profile in rats with a 4.4 h half-life, 56 μM peak plasma concentration, and 89% bioavailability.