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Subsequent optimization of 17 through incorporating an oxetane moiety into the tetrahydropyridine scaffold resulted in compound 18 (AS-1763), which demonstrated superior potency against wild-type and mutant BTK (IC 50 = 0.85 and 0.99 nM, respectively), the highest cellular activity (IC 50 = 2 nM for OCI-Ly10 cells), and substantially improved permeability (P app = 1.42 × 10 −6 cm/s)

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Accumulating evidence suggests that ROS are not only toxic by-products of cellular metabolism but also essential participants in cell signaling and regulation (84)