Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor used to treat chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). Both MCL and CLL are B-cell non-Hodgkin's lymphomas, which are refractory and easy to relapse. Commonly used chemotherapy and immunotherapy are not targeted, and grade 3 or 4 adverse reactions often occur. Ibrutinib can be targeted to bind with BTK necessary for the formation, differentiation, information transmission and survival of B lymphocytes, irreversibly inhibit the activity of BTK, and effectively inhibit the proliferation and survival of tumor cells; and it is absorbed rapidly after oral administration, 1~ The maximum blood drug concentration reached 2 hours, and the adverse reaction is classified as 1 or 2, which will become a new choice for the treatment of CLL and MCL.

Ibrutinib is a highly selective Bruton's tyrosine kinase (Btk) irreversible inhibitor.PCI-32765 (Ibrutinib) is a selective and irreversible pyrrolopyrimidine-based inhibitor of BTK with IC50 of 0.5 nM. [1] PCI-32765 binds irreversibly to Cys-481 in BTK and thus is only active with other kinases with such a modifiable cysteine residue. In DOHH2 cells, in which the BCR pathway can be activated by anti-IgG, PCI-32765 inhibits autophosphorylation of BTK (IC50, 11 nM), BTK's physiological substrate, PLCg (IC50, 29 nm), and downstream ERK (IC50, 13 nm). 

PCI-32765 (Ibrutinib) may be an important new targeted treatment approach for CLL pts. In ex vivo assays with whole bold, PCI-32765 (Ibrutinib) prevents the activation of human BCR with an IC50 of about 0.2 μM, while not influencing the activation of T cell. Treatment of CD40 or BCR activated CLL cells with PCI-32765 (Ibrutinib) results in inhibition of BTK tyrosine phosphorylation and also effectively abrogates downstream survival pathways activated by this kinase including ERK1/2, PI3K, and NF-κB. In addition, PCI-32765 (Ibrutinib) prevents activation-induced proliferation of CLL cells in vitro, and effectively inhibits survival signals provided externally to CLL cells from the microenvironment including soluble factors (CD40L, BAFF, IL-6, IL-4, and TNF-α), fibronectin engagement, and stromal cell contact. PCI-32765 is originally developed by Pharmacyclics. And participants is been invited for the phase I clinical trials.