BET-IN-13

BET-IN-13 is a potent BET inhibitor with an IC50 value of 1.6 nM. BET-IN-13 reduces LPS-induced TNF-α, IL-1β, IL-6, and NOS2 mRNA expression levels. BET-IN-13 shows anti-inflammatory activity. BET-IN-13 has the potential for the research of acute liver injury[1].

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Epigenetics >> Epigenetic Reader Domain

BRD4 BD1:57.4 nM (IC50)

BRD4 BD2:44.4 nM (IC50)

BRD2 BD1:79.3 nM (IC50)

BRD2 BD2:27.5 nM (IC50)

BRD3 BD1:45.6 nM (IC50)

BRD3 BD2:18.9 nM (IC50)

BRDT BD1:87.0 nM (IC50)

BRDT BD2:43.4 nM (IC50)

BET-IN-13 (compound 28) (1.1, 3.3, 10 µM, 2+6 h) 降低 RAW264.7 细胞中 LPS (500 ng/ml) 诱导的 TNF-α、IL-1β、IL-6 和 NOS2 mRNA 的表达水平[1]。 RT-PCR[1] Cell Line: RAW264.7 cells Concentration: 1.1, 3.3, 10 µM Incubation Time: Pre-treated for 2 h before stimulating with LPS for 6 h Result: Significantly reduced LPS (500 ng/ml) induced TNF-α, IL-1β, IL-6 and NOS2 mRNA expression levels in a dose-dependent manner.

BET-IN-13 (3 mg/kg；静脉注射；一次) 在小鼠中显示出良好的药代动力学 (PK) 特性，T1/2 为 0.69 h，AUCINF-obs 为 609 h*ng/mL 和 Vss 为 1717 mL/kg[1]。 BET-IN-13 (37.5、75 mg/kg；腹腔注射；一次) 降低 LPS/D-GalN(d-gaiactosamine)诱导的急性肝衰竭 (ALF) 小鼠的炎症和肝损伤而无明显毒性[1]。 Animal Model: 20-22g, Female C57BL/6J mice (LPS/D-GalN(d-gaiactosamine)-induced acute liver failure (ALF))[1] Dosage: 37.5, 75 mg/kg Administration: I.p.; once Result: Reduced inflammatory responses associated with LPS/GalN-induced acute liver failure with the survival rate increased significantly to 69.2% for37.5 mg/kg and to 84.6% for 75 mg/kg.

[1]. Chen C, et al. Cyclization strategy leads to highly potent Bromodomain and extra-terminal (BET) Bromodomain inhibitors for the treatment of acute liver injury. Eur J Med Chem. 2022 Dec 16;247:115023.