Fenebrutinib

Fenebrutinib (GDC-0853) is a potent, selective, orally available, and noncovalent bruton's tyrosine kinase (Btk) inhibitor with K_is of 0.91 nM, 1.6, 1.3, 12.6, and 3.4 nM for WT Btk, and the C481S, C481R, T474I, T474M mutants. Fenebrutinib has the potential for rheumatoid arthritis and systemic lupus erythematosus research^[1]. IC50 & Target: Ki: 0.91 nM (Btk WT), 1.6 nM (Btk C481S), 1.3 nM (Btk C481R), 12.6 nM (Btk T474I), and 3.4 nM (Btk T474M)^[1] In Vitro: Fenebrutinib (GDC-0853) inhibits CD69 expression on CD19⁺ B cells in human whole blood with an IC₅₀ of 8.4±5.6 nM. Fenebrutinib inhibits CD63 expression on basophils with an IC₅₀ of 30.7±4.1 nM^[2].
Fenebrutinib suppresses anti-IgM induced Btk Y223 autophosphorylation in human whole blood (IC₅₀=11 nM)^[2]. In Vivo: Fenebrutinib (GDC-0853) dose-dependently reduces ankle thickness following once (0.06, 0.25, 1, 4, and 16 mg/kg QD; orally) or twice (0.125, 0.5, and 2 mg/kg BID; orally) daily in female Lewis rats with developing collagen-induced arthritis^[2].
Fenebrutinib (0.2 mg/kg IV and 1.0 mg/kg PO; for rats) and (0.2 mg/kg IV and 0.5 mg/kg PO for dogs) demonstrates the half-lives (t_1/2s) of 2.2 and 3.8 h In rats, and dogs, respectively^[2].