5.33060

HMGB Inhibitor, Inflachromene

• Synonyme(s) : HMGB Inhibitor, Inflachromene, Neuroinflammatory Inhibitor, Inflachromene, HMGB2 Inhibitor, Inflachromene, 10-Hydroxy-7,7-dimethyl-2-phenyl-7,12b-dihydrochromeno[4,3-c][1,2,4]triazolo[1,2-a]pyridazine-1,3(2H,5H)-dione
• Formule empirique (notation de Hill): C₂₁H₁₉N₃O₄
• Poids moléculaire : 377.39
• Code UNSPSC : 12352200
• ID de substance PubChem : 49857340

Propriétés

• Pureté: ≥98% (HPLC)
• Niveau de qualité: 100
• Forme: solid
• Fabricant/nom de marque: Calbiochem^®
• Conditions de stockage: OK to freeze; protect from light
• Couleur: off-white
• Solubilité: DMSO: 50 mg/mL
• Température de stockage: −20°C
• Chaîne SMILES: CC1(C2=CCN3C(=O)N(C(=O)N3C2C4=C(O1)C=C(C=C4)O)C5=CC=CC=C5)C

Description

Description générale

A cell-permeable, chromene-fused benzopyran-embedded tetracyclic compound that selectively and directly binds to the DNA binding domain box A of high mobility group box (HMGB) proteins and blocks their post-translational phosphorylation and acetylation. Diminishes the cytoplasmic accumulation of HMGB2 in microglial cells. Blocks lipopolysaccharide (LPS)-induced nitrite release in BV-2 microglial cells, RAW 264.7 macrophages, and mouse primary microglial cultures (~50 nM to 20 µM) without inducing any toxicity. However, it is shown to be less potent in primary astrocytes. Suppresses LPS-stimulated increase in the levels of IL-6, IL-1b, NOS2, and TNFα genes and inhibits the nuclear translocation of NF-κB. Also shown to reduce LPS-induced phosphorylation of ERK, JNK, and p38 MAP kinases in microglia. Reduces neuroinflammation, neurite damage, and spinal cord demyelination in a murine model of auto-immune encephalitis (~10 mg/kg).

A cell-permeable, chromene-fused benzopyran-embedded tetracyclic compound that selectively and directly binds to the DNA binding domain box A of high mobility group box (HMGB) proteins and blocks their post-translational phosphorylation and acetylation. Diminishes the cytoplasmic accumulation of HMGB2 in microglial cells. Blocks lipopolysaccharide (LPS)-induced nitrite release in BV-2 microglial cells, RAW 264.7 macrophages, and mouse primary microglial cultures (~50 nM to 20 µM) without inducing any toxicity. However, it is shown to be less potent in primary astrocytes. Suppresses LPS-stimulated increase in the levels of IL-6, IL-1b, NOS2, and TNFα genes and inhibits the nuclear translocation of NF-κB. Also shown to reduce LPS-induced phosphorylation of ERK, JNK, and p38 MAP kinases in microglia. Reduces neuroinflammation, neurite damage, and spinal cord demyelination in a murine model of auto-immune encephalitis (~10 mg/kg).

Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.

Actions biochimiques/physiologiques

Cell permeable: yes

Primary Target
HMGB2

Reversible: yes

Conditionnement

Packaged under inert gas

Avertissement

Toxicity: Standard Handling (A)

Reconstitution

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

Autres remarques

Lee, S., et al. 2014. Nat. Chem. Biol.10, in press.

Informations légales

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

Informations sur la sécurité

• Code de la classe de stockage: 11 - Combustible Solids
• Classe de danger pour l'eau (WGK): WGK 3
• Point d'éclair (°F): Not applicable
• Point d'éclair (°C): Not applicable