Pirtobrutinib

DB17472ApprovedInvestigationalSmall moleculeKinase Inhibitor

Pirtobrutinib is a kinase inhibitor used to treat relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy. It is also used in adults with relapsed or refractory CLL/SLL who have previously received a covalent BTK inhibitor. Pirtobrutinib is a small molecule and a highly selective non-covalent inhibitor of Bruton’s tyrosine kinase (BTK).

Mechanism: Bruton’s tyrosine kinase (BTK) is a tyrosine kinase located in the cytoplasm that is recruited to the cytoplasm upon activation. In B-cells, BTK participates in the activation of B-cell antigen receptor (BCR) signaling and cytokine receptor pathways, both critical for B-cell development, function, adhesion and migration. Therefore, the inhibition of BTK is a valuable target for the treatment of B-cell cancers. Pirtobrutinib binds to Bruton’s tyrosine kinase (BTK) in a non-covalent manner and inhibits its activity. Unlike other BTK inhibitors that bind covalently to the active site of BTK, the inhibitory activity of pirtobrutinib is maintained even in the presence of mutations in this region, such as the presence of Cys481. In nonclinical studies, pirtobrutinib inhibited BTK-mediated B-cell CD69 expression and inhibited malignant B-cell proliferation.
Curator reviewed · 5 references
Primary indication: Pirtobrutinib is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.Curator reviewed · 10 structured indications
Formula / weight: C₂₂H₂₁F₄N₅O₃ · 479.436 g/mol (avg)
First approval: Canada, 2025 · United States, 2023 · European Union, 2023
Code names: LOXO-305 · LY-3527727 · RXC-005
Brand names: Jaypirca