Nurr1/NR4A2 Agonist

Amodiaquine (Amodiaquin), a 4-aminoquinoline class of antimalarial agent, is a potent and orally active histamine N-methyltransferase inhibitor. Amodiaquine is also a Nurr1 agonist and specifically binds to Nurr1-LBD (ligand binding domain) with an EC₅₀ of ~20 μM. Anti-inflammatory effect.

Amodiaquine dihydrochloride dihydrate (Amodiaquin dihydrochloride dihydrate), a 4-aminoquinoline class of antimalarial agent, is a potent and orally active histamine N-methyltransferase inhibitor. Amodiaquine dihydrochloride dihydrate is also a Nurr1 agonist and specifically binds to Nurr1-LBD (ligand binding domain) with an EC₅₀ of ~20 μM. Anti-inflammatory effect.

Amodiaquine dihydrochloride (Amodiaquin dihydrochloride), a 4-aminoquinoline class of antimalarial agent, is a potent and orally active histamine N-methyltransferase inhibitor with a K_i of 18.6 nM. Amodiaquine dihydrochloride is also a Nurr1 agonist and specifically binds to Nurr1-LBD (ligand binding domain) with an EC₅₀ of ~20 μM. Anti-inflammatory effect.

Nurr1 inverse agonist-1 is an inverse agonist tool for the neuroprotective transcription factor Nurr1.

Nurr1 agonist 2 (Compound 7) is a Nurr1 agonist (EC₅₀: 0.07 μM). Nurr1 agonist 2 binds to the recombinant Nurr1 ligand binding domain (LBD) with a K_d value of 0.14 μM. Nurr1 agonist 2 increases the Nurr1-regulated genes tyrosine hydroxylase (TH) and vesicular amino acid transporter 2 (VMAT2) mRNA expression.

Nurr1 agonist 12 (Compound 37) is the agonist for nuclear receptor-associated protein 1 (Nurr1) that activates the transcriptional activity of Nurr1 with an EC₅₀ of 0.06 μM. Nurr1 agonist 12 activates the human response elements NBRE, NurRE, and DR5 with EC₅₀ of 0.07 μM, 0.027 μM, and 0.014 μM, respectively. Nurr1 agonist 12 induces the expression of Nurr1-regulated neurotrophic genes, such as tyrosine hydroxylase (TH), SOD1/2, BDNF, Sestrin 3, and BIRC5 (Survivin). Nurr1 agonist 12 exhibits neuroprotective efficacy against Paraquat-induced neurotoxicity.

Nurr1 agonist 14 (Compound 32) is a Nurr1 agonist with an EC₅₀ of 0.09  μM for Nurr1. Nurr1 agonist 14 has significant neuroprotective activity with no influence of residual DHODH inhibition. Nurr1 agonist 14 upregulates neuroprotective genes including SOD2, SESN3, BIRC5, XIAP, FLRT2 and CRMP4 in dopaminergic neurons. Nurr1 agonist 14 can be used for neurodegenerative diseases such as Alzheimer′s disease (AD), Parkinson′s disease (PD) and multiple sclerosis (MS) research.

Nurr1 agonist 9 (Compound 36) is an agonist for Nurr1 with an EC₅₀ of 0.090 µM and a K_d of 0.17 µM. Nurr1 agonist 9 activates the Nurr1 homodimer (NurRE, EC₅₀=0.094 µM) and the Nurr1-RXR heterodimer (DR5, EC₅₀=0.165 µM). Nurr1 agonist 9 induces the expression of Nurr1-regulated tyrosine hydroxylase (TH) in organoid Parkinson's Disease model. Nurr1 agonist 9 is human brain endothelial cell barrier prmeable.

Nurr1 agonist 13 (Compound 1) is a potent nuclear receptor related 1 (Nurr1, NR4A2) agonist with an EC₅₀ value of 0.06 μM. Nurr1 agonist 13 is promising for research of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and multiple sclerosis.

Nurr1 agonist 10 (compound 37) is a potent Nurr1 agonist with an EC₅₀ value of 40 nM. Nurr1 agonist 10 has the potential for the research of Parkinson’s and Alzheimer’s disease.

Nurr1 agonist 5 (compound 5o) is a neuroprotective transcription factor Nurr1 agonist with a K_d of 0.5 μM and an EC₅₀ of 3 μM.

NR4A agonist-2 is a selective pan-NR4A agonist designed based on Vidofludimus (HY-14908), with a K_d of 0.10 μM against NR4A1, and EC₅₀ values of 0.098 μM, 0.092 μM and 0.09 μM against Nur77, Nurr1, NOR-1, respectively. NR4A agonist-2 exhibits 47-fold selectivity over DHODH, and shows no cytotoxic activity at concentrations up to 10 μM. By binding to a specific surface pocket in the ligand-binding domain of Nurr1, NR4A agonist-2 inhibits the formation of Nurr1 homodimers, activates response elements such as NBRE, NurRE, DR5, and then potently induces the expression of neuroprotective genes including BDNF, SOD2, thereby exerting neuroprotective activity. NR4A agonist-2 can be used in the research of neurodegenerative diseases such as Parkinson's disease, dementia and multiple sclerosis.