How does zanubrutinib differ from ibrutinib in pharmacokinetics and target occupancy?
Zanubrutinib has a more-specific target binding profile than ibrutinib. It binds to BTK at least as potently as ibrutinib. Zanubrutinib has fewer off-target effects on related enzymes, including the epidermal growth factor receptor (EGFR), interleukin 2–inducible T-cell kinase (ITK), Janus kinase 3 (JAK3), human epidermal growth factor receptor 2 (HER2), and tyrosine kinase expressed in hematopoietic carcinoma (TEC).
There is the potential that zanubrutinib can hit BTK with fewer off-target side effects. For example, it is thought that the rash and diarrhea sometimes seen with ibrutinib may be related to EGFR blockade. Ibrutinib may not combine well with monoclonal antibodies, such as rituximab (Rituxan, Genentech/Biogen), because of ITK effects on the immune effector cells. Zanubrutinib has the potential to target BTK with fewer off-target side effects, and it may combine better with monoclonal antibodies.
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