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). [1]


Additionally, PCI-32765 has been shown in CD40- or BCR-activated chronic lymphocytic leukemia cells to inhibit ERK1/2, PI3K, and NFkB. [2] PCI-32765 is efficacious in collagen-induced arthritis models in a dose dependent manner, reversing inflammation at an ED50 of 2.6 mg/kg/day. [3]. PCI-32765 also inhibits BCR-activated primary B-cell proliferation at an IC50 of 8 nM. [3]

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). [1]


Additionally, PCI-32765 has been shown in CD40- or BCR-activated chronic lymphocytic leukemia cells to inhibit ERK1/2, PI3K, and NFkB. [2] PCI-32765 is efficacious in collagen-induced arthritis models in a dose dependent manner, reversing inflammation at an ED50 of 2.6 mg/kg/day. [3]. PCI-32765 also inhibits BCR-activated primary B-cell proliferation at an IC50 of 8 nM. [3]