BI 653048 (phosphate)

BI 653048 phosphate is a selective and orally active nonsteroidal glucocorticoid (GC) agonist with an IC₅₀ value of 55 nM^[1]. BI 653048 phosphate inhibits CP1A2, CYP2D6, CYP2C9, CYP2C19 and CYP3A4 isoforms’ activity and reduces affinity for the hERG ion channel (IC₅₀>30 μM)^[2]. BI 653048 phosphate is extracted from patent WO2005028501A1 (Compound 103), is also a HCV NS3 protease inhibitor that can reduce viral loads infected with the hepatitis C virus^[3]. In Vitro:BI 653048 phosphate exhibits an improved drug-like properties, inhibits CP1A2 ,CYP2D6 ,CYP2C9, CYP2C19 and CYP3A4 with IC₅₀ values of 50 μM, 41 μM, 12 μM, 9 μM,and 8 μM, respectively^[2].
BI 653048 phosphate reduces affinity for the hERG ion channel with an IC₅₀>30 μM in recombinant HEK293 cells expressing the human ERG potassium channel^[2].
BI 653048 phosphate inhibits TNF-stimulated IL-6 production in mouse RAW cells with an IC₅₀ value of 100 nM^[2].
In Vivo:BI 653048 phosphate (oral administration; 3, 10, and 30 mg/kg) at 3 mg/kg has nonsignificant decreases for all measured histology parameters (ankle inflammation, pannus formation, cartilage damage, and bone resorption), Mid-dose (10 mg/kg) treatment significantly decreases pannus and bone resorption (33%) as well as summed scores (27%), while at high dose (30 mg/kg), all parameters are significantly decreased (87-96%). The ED₅₀ value for the summed scores is 14 mg/kg^[2].