Pirtobrutinib is an oral, reversible, non‑covalent BTK inhibitor. It binds to the ATP‑binding pocket of BTK without relying on the C481 residue, making it active against both wild‑type BTK and C481‑mutated BTK (a common resistance mechanism to covalent BTK inhibitors like ibrutinib).
Approved Indications
Relapsed or refractory mantle cell lymphoma (MCL) in adults after ≥2 prior systemic therapies, including a BTK inhibitor
Relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) in adults previously treated with a covalent BTK inhibitor
Key Advantages
Overcomes C481 resistance: Effective in patients who failed covalent BTK inhibitors
High selectivity: >300‑fold selectivity for BTK over most other kinases
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