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Biophysical confirmation of covalent binding is also an important step in the ongoing industrial efforts to develop covalent kinase inhibitors with an improved selectivity/potency profile, as illustrated by intact protein analysis of covalent adducts between the BTK kinase domain and clinical candidates evobrutinib (Merck) [86], remibrutinib (Novartis) [87], and tirabrutinib (Ono Pharmaceutical/Gilead Sciences) [88]
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