Biochemical Characterization of Tirabrutinib and Other Irreversible Inhibitors of Bruton's Tyrosine Kinase (BTK) Reveals Differences in On - and Off – Target Inhibition

Albert Liclican, Loredana Serafini, Weimei Xing, Gregg Czerwieniec, Bart Steiner, Ting Wang, Katherine M. Brendza1, Justin D. Lutz, Kathleen S. Keegan, Adrian S. Ray2, Brian E. Schultz, Roman Sakowicz, Joy Y. Feng⁎

Gilead Sciences Inc, 333 Lakeside Drive, Foster City, CA 94404, United States of America

Conclusions: For the BTK inhibitors tested in this study, analysis of the inactivation kinetics yielded a more accurate measurement of potency and selectivity than conventional single-time point inhibition measurements. Subtle but clear differences were identified between clinically tested BTK inhibitors which may translate into differentiated clinical efficacy and safety.”

Biochemical characterization of tirabrutinib and other irreversible inhibitors of Brutons tyrosine kinase (BTK) reveals differences in on - and off - target inhibition_Page_1