Zebutinib is a novel BTK inhibitor that inhibits BTK activity by covalently binding to cysteine at position 481 of the BTK protein, thereby suppressing tyrosine phosphorylation at position 233.
1、 Indications
This single drug is suitable for:
1) Adult patients with mantle cell lymphoma (MCL) who have received at least one treatment in the past.
2) Adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
3) Adult patients with Fahrenheit macroglobulinemia (WM).
This product, in combination with Ottuzumab, is suitable for:
Adult patients with recurrent or refractory follicular lymphoma (FL) who have received at least second-line systemic treatment in the past.
2、 Usage and dosage
Administer orally before or after meals. The recommended daily total dose is 320mg, with a dosing regimen of 160mg each time (2 80mg capsules), twice daily, until disease progression or intolerable toxicity occurs.
3、 Mechanism of action
Zebutinib is a selective inhibitor of Bruton's tyrosine kinase (BTK), which covalently binds to cysteine at position 481 of the BTK protein to inhibit its tyrosine phosphorylation at position 223, thereby suppressing BTK activity. BTK is a key regulatory factor in the B cell receptor (BCR) signaling pathway, playing an important role in B cell proliferation, apoptosis, differentiation, and development. In non clinical studies, Zebutinib inhibits malignant B cell proliferation and tumor growth。
BTK is a key regulatory factor in the B cell receptor (BCR) signaling pathway, involved in the proliferation, transport, chemotaxis, and adhesion of B cells, and widely expressed in different types of hematological malignancies.
4、 Drug interactions
The effect of CYP3A inhibitors on Zebutinib
CYP3A inducer: Combination use of multiple doses of rifampicin (strong CYP3A inducer) reduced the Cmax of Zebutinib by 92%, with an AUC of 93%.
The combined use of multiple doses of efavirenz (moderate CYP3A inducer) was predicted to result in a Cmax of 58% and an AUC of 60% for Zebutinib.
CYP3A substrate: The combined use of multiple doses of Zebutinib reduces the Cmax of Midazolam (CYP3A substrate) by 30% and AUC by 47%.
CYP2C19 substrate: The combined use of multiple doses of Zebutinib reduces the Cmax and AUC of omeprazole (CYP2C19 substrate) by 20% and 36%, respectively.
Transport system: The combined use of multiple doses of Zebutinib increases the Cmax of digoxin (P-gp substrate) by 34% and AUC by 11%. There is no significant difference in clinical practice.
