Figure 3.

The residency time of BTK inhibitors in the kinase pocket dictates potency against distal B‐cell pharmacodynamic responses. (a) Dot plot showing IC₅₀ values for constitutive BTK phosphorylation in unstimulated cells (pBTK, x‐axis) and CD69 expression in anti‐IgD‐stimulated B cells (CD69, y‐axis) in whole blood (WB) assays. Data from n = 420 Biogen‐reversible BTK inhibitors are shown with BIIB091 and BIIB068 (early generation BTK inhibitor ¹¹ ) highlighted in red and blue, respectively. Dashed lines indicate the equal potency line and the 10‐fold deviation from the equipotency line. (b, c) Dot plots showing plasma protein binding‐corrected IC₅₀ values for constitutive BTK phosphorylation in unstimulated cells (b) and CD69 expression in anti‐IgD‐stimulated B cells (c) against the half‐life of the BTK:BTK inhibitor complex measured by surface plasmon resonance. Data from n = 30 Biogen‐reversible BTK inhibitors are shown.