Recent Progress of Irreversible BTK Inhibitors

In recent years, Bruton tyrosine kinase (BTK) inhibitors that selectively inhibit B cell receptor (BCR) signaling have become a popular and effective treatment for lymphomas in the public. As the pivotal tyrosine kinase BTK regulates the BCR pathway, BTK inhibitors were developed to block the pathway by binding with BTK thereby relieving the B-cell lymphoma progression. Ibrutinib, the first-generation BTK inhibitor, can effectively inhibit BTK and alleviate various cancer diseases. However, ibrutinib's lack of selectivity has led to a series of side effects, having adverse effects on survival rates and tolerability. By altering the molecular structure, researchers have developed the next-generation irreversible BTK inhibitors aiming at increasing target specificity and decreasing off-target impacts, such as acalabrutinib, tirabrutinib, spebrutinib, branebrutinib, and zanubrutinib, who recently received approval by FDA. This article compares and analyzes the advantages and disadvantages of these irreversible BTK inhibitors, especially zanubrutinib, with ibrutinib and finally draws a conclusion.