Activateur Nurr1 ; ipsoc 1 pc x 10 MG

Non disponible en dehors du Royaume-Uni et de l'Irlande

Biochem/physiol Actions

Primary TargetNurr1/NR4A2

Cell permeable: yes

General description

A cell-permeable, isoxazolopyridinone compound that acts as a potent activator of Nurr1/NR4A2-dependent transcription activity in reporter assays using Nurr1-expressing murine midbrain dopaminergic neuronal cell line MN9D (EC₅₀ = 3.9 nM, E_max = 2.1-fold of basal activity) and exhibits oral availability as well as blood-brain-barrier permeability in mice. Preventive treatment (10 mg/kg/12h from 7th to 23rd day post MOG_35-55 immunization) is shown to delay the onset (15 d.p.i. with & 12 d.p.i. without preventive treatment) and severity of experimental autoimmune encephalomyelitis (EAE) in a murine multiple sclerosis (MS) model in vivo, while no improvement of EAE symptoms is observed if the treatment starts after the disease onset (10 mg/kg/12h from 21 d.p.i. to 36 d.p.i.). Consistent with the known negative regulating role of Nurr1 against NF-κB pathway, preventive treatment is shown to result in significantly reduced expression of 16 NF-κB pathway genes in the spinal cord of EAE mice.

A cell-permeable, isoxazolopyridinone compound that acts as a potent activator of Nurr1/NR4A2-dependent transcription activity in reporter assays using Nurr1-expressing murine midbrain dopaminergic neuronal cell line MN9D (EC₅₀ = 3.9 nM, E_max = 2.1-fold of basal activity) and exhibits oral availability as well as blood-brain-barrier permeability in mice. Preventive treatment (10 mg/kg/12h from 7th to 23rd day post MOG_35-55 immunization) is shown to delay the onset (15 d.p.i. with & 12 d.p.i. without preventive treatment) and severity of experimental autoimmune encephalomyelitis (EAE) in a murine multiple sclerosis (MS) model in vivo, while no improvement of EAE symptoms is observed if the treatment starts after the disease onset (10 mg/kg/12h from 21 d.p.i. to 36 d.p.i.). Consistent with the known negative regulating role of Nurr1 against NF-κB pathway, preventive treatment is shown to result in significantly reduced expression of 16 NF-κB pathway genes in the spinal cord of EAE mice.Please note that the molecular weight for this compound is batch-specific due to variable water content.

A cell-permeable, blood-brain barrier permeable, potent activator of Nurr1/NR4A2-dependent transcription activity in (EC₅₀ = 3.9 nM in MN90 cell line).

Legal Information

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Other Notes

Montarolo, F., 2014. PLoS One.9, e108791.Hintermann, S., et al. 2007. Bioorg. Med. Chem. Lett.17, 193.

Packaging

10 mg in Glass bottle

Reconstitution

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Use only fresh DMSO for reconstitution.

Warning

Toxicity: Standard Handling (A)