5.33169

BET Inhibitor, I-BET726

• Sinónimos: BET Inhibitor, I-BET726, BET Inhibitor, BET726, GSK1324726A, 4-((2S,4R)-1-Acetyl-4-((4-chlorophenyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid
• Fórmula empírica (notación de Hill): C₂₅H₂₃ClN₂O₃
• Número de CAS: 1300031-52-0
• Peso molecular: 434.91
• UNSPSC Code: 12352200
• NACRES: NA.77

Propiedades

• assay: ≥98% (HPLC)
• Quality Level: 100
• form: solid
• manufacturer/tradename: Calbiochem^®
• storage condition: OK to freeze; protect from light
• color: light yellow
• solubility: DMSO: 50 mg/mL
• storage temp.: −20°C

Descripción

General description

A cell-permeable tetrahydroquinoline based compound that acts as a highly potent and selective inhibitor of bromodomain and extra-terminal (BET) family proteins (IC₅₀ = 41, 31, and 22 nM for BRD2, BRD3, BRD4, respectively). Binds to the acetyl-lysine recognition pocket of BET proteins and competes with tetra-acetylated histone H4 peptides (K5ac, K8ac, K12ac, K16ac) for binding to the bromodomains of these proteins. Does not affect the activity of over 50 different receptors, ion channels, and transporters even at higher concentrations (1-10 µM). Exhibits cytotoxicity towards neuroblastoma cell lines, induces apoptosis, and inhibits their growth (gIC₅₀ = 26 and 60 nM for CHP-212 and SK-N-AS cells, respectively). Suppresses the growth of human neuroblastoma xenografts in murine models (5 mg/kg, p.o. for 2 weeks) and reduces the expression of MYCN and BCL2. Shown to improve survival rate of Balb/c mice subjected to LPS-induced (15 - 20 mg/kg) septic shock (10 mg/kg, i.v.). Displays desirable pharmacokinetic properties (t1/2 = 3.6 h; AUC 0-t = 6.03 µg/h/ml at 10 mg/kg i.v. in mice).

A cell-permeable tetrahydroquinoline based compound that acts as a highly potent and selective inhibitor of bromodomain and extra-terminal (BET) family proteins (IC₅₀ = 41, 31, and 22 nM for BRD2, BRD3, BRD4, respectively). Binds to the acetyl-lysine recognition pocket of BET proteins and competes with tetra-acetylated histone H4 peptides (K5ac, K8ac, K12ac, K16ac) for binding to the bromodomains of these proteins. Does not affect the activity of over 50 different receptors, ion channels, and transporters even at higher concentrations (1-10 µM). Exhibits cytotoxicity towards neuroblastoma cell lines, induces apoptosis, and inhibits their growth (gIC₅₀ = 26 and 60 nM for CHP-212 and SK-N-AS cells, respectively). Suppresses the growth of human neuroblastoma xenografts in murine models (5 mg/kg, p.o. for 2 weeks) and reduces the expression of MYCN and BCL2. Shown to improve survival rate of Balb/c mice subjected to LPS-induced (15 - 20 mg/kg) septic shock (10 mg/kg, i.v.). Displays desirable pharmacokinetic properties (t1/2 = 3.6 h; AUC 0-t = 6.03 µg/h/ml at 10 mg/kg i.v. in mice).

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.

BET Inhibitor, I-BET726, is a cell-permeable, potent, and selective inhibitor of BET family proteins (IC₅₀ = 41, 31, and 22 nM for BRD2, BRD3, BRD4, respectively).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
BET

Target IC₅₀: 41 nM, 31 nM, and 22 nM for BRD2, BRD3, BRD4, BRDT respectively

Target K_i: 4.4 nM for BRD4

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Other Notes

Gosmini, R., et al. 2014. J. Med. Chem.57, 811.
Wyce, A., et al. 2013. Plos One.8, e72967.

Legal Information

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

Información de seguridad

• Storage Class: 11 - Combustible Solids
• wgk_germany: WGK 3
• flash_point_f: Not applicable
• flash_point_c: Not applicable