Spebrutinib (besylate)

Spebrutinib besylate (AVL-292 benzenesulfonate; CC-292 besylate) is a potent inhibitor of Btk kinase activity (IC₅₀<0.5 nM, K_inact/K_i=7.69×10⁴ M^-1s^-1s) in biochemical assays. IC50 & Target: IC50: <0.5 nM (Btk)^[1] In Vitro: Spebrutinib (CC-292) is a covalent, highly selective, orally active inhibitor of Btk with IC₅₀ value of 0.5 nM. Spebrutinib also less potently inhibits Yes, c-Src, Brk, Lyn, and Fyn with IC₅₀s of 723 nM, 1.729 μM, 2.43 μM, 4.4 μM, and 7.15 μM, rspectively. Extensive analysis has revealed that the EC₅₀ of Btk occupancy from a Spebrutinib dose-response in Ramos cells (EC₅₀=6 nM) correlated directly with the cellular EC₅₀ of Btk kinase inhibition with Spebrutinib (EC₅₀=8 nM). Furthermore, the concentration at which Spebrutinib inhibits 90% of Btk activity in Ramos cells is 35 nM while the concentration of Spebrutinib required for 90% occupancy of Btk is 39 nM^[1].