Background:

PCI-32765 is an inhibitor of Bruton tyrosine kinase (BTK) with IC50 value of 0.5nM [1].

PCI-32765 is a covalent and irreversible inhibitor of BTK through bonding to Cys-481 in the ATP binding domain. PCI-32765 inhibits phosphorylation of BTK in a B cells (IC50 of 11nM) as well as the downstream substrates phosphoinositide phospholipase Cγ (PLC γ) and ERK in cell assays. PCI-32765 has in vivo efficacy in B cell lymphoma. In CLL cells, PCI-32765 induces cells apoptosis through inhibiting the expression of BCR-dependent UDP-glucose ceramide glucosyltransferase [1].

PCI-32765 is oral effective in vivo. It induces lymphocytosis during the first weeks of therapy in patients with CLL. It is also efficacious in autoimmune disease. In the MRL-Fas lupus model, PCI-32765 inhibits collagen-induced arthritis as well as autoantibody production and development of kidney disease. It also diminished FcγRIII-induced production of pro-inflammatory cytokines [1].

参考文献:
[1] Burger JA, Buggy JJ. Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765). Leuk Lymphoma. 2013 Nov;54(11):2385-91.