BTK Inhibition and the Mechanism of Action of Ibrutinib
Jennifer Woyach, MD, discusses Bruton's tyrosine kinase inhibition and the mechanism of action of ibrutinib.
Jennifer Woyach, MD, Assistant Professor of Internal Medicine, Division of Hematology, The Ohio State University Comprehensive Cancer Center, discusses Bruton's tyrosine kinase (BTK) inhibition and the mechanism of action of ibrutinib.
BTK is not found to be recurrently mutated in chronic lymphocytic leukemia‎ (CLL), but it is overexpressed at the transcript level. At the protein level, Woyach says, it is slightly more variable but is seen to be overexpressed in many patients. BTK and other members of the pathway are constitutively phosphorylated in this disease, likely causing activation and accumulation of downstream targets.
Clinical Pearls
Ibrutinib binds to BTK at the cysteine-481 residue, which is in the active site, preventing kinase activity of BTK. Ibrutinib is an irreversible covalent inhibitor, meaning that after the drug is metabolized, BTK should still be inhibited.
- BTK is not found to be recurrently mutated in CLL, but it is overexpressed at the transcript level in CLL
- BTK and other members of the pathway are constitutively phosphorylated, likely causing activation of downstream targets
Clinical Pearls II
- Ibrutinib binds to BTK at the cysteine-481 residue
- Ibrutinib is an irreversible covalent inhibitor
Considering the Durability of Zanubrutinib in Relapsed/Refractory CLL
April 11th 2024During a Case-Based Roundtable® event, Marc S. Hoffmann, MD, discussed his viewpoints on the use of Bruton tyrosine kinase inhibitors for patients with relapsed/refractory chronic lymphocytic leukemia and the efficacy behind zanubrutinib in the second article of a 2-part series.
Read More
