Mechanism of Action

Ibrutinib works differently than existing chemotherapy and immunotherapy

Ibrutinib is a small molecule that works by inhibiting a type of enzyme, called a protein kinase, that controls the rate at which certain cells multiply. In particular, ibrutinib has been shown to covalently bind to, and ultimately inhibit, the Bruton’s tyrosine kinase (BTK).1,2 While BTK plays a primary role in signaling healthy B cells to mature, release antibodies and proliferate, B-cell cancers (which include chronic lymphocytic leukemia and most non-Hodgkin’s lymphomas) also depend on BTK in the same way to survive.3

Nonclinical studies have shown that BTK inhibition prevents tumor cell adhesion, migration and homing (returning to lymph organs to proliferate), along with increase in cancer cell apoptosis (programmed cell death) and inhibition of proliferation.3-5

In addition to its role in B-cell malignancies, the mechanistic role of BTK and ibrutinib has also been evaluated in other cell types such as mast cells, monocytes and macrophages.6-9

We are committed to fully researching the potential of BTK inhibition for patients, as well as the discovery of new small molecules therapies in the future.

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 References: 1) Burger JA, Buggy JJ. Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765). Leuk Lymphoma. 2013;54(11):2385-2391. 2) Honigberg LA, Smith AM, Sirisawad M, et al. The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy. Proc Natl Acad Sci U S A. 2010;107(29):13075-13080. 3) Cinar M, Hamedani F, Mo Z, Cinar B, Amin HM, Alkan S. Bruton tyrosine kinase is commonly overexpressed in mantle cell lymphoma and its attenuation by ibrutinib induces apoptosis. Leuk Res. 2013;37(10):1271-1277. 4) Ponader S, Chen S-S, Buggy JJ, et al. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. 2012;119(5):1182-1189. 5) Herman SEM, Gordon AL, Hertlein E, et al. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011;117(23):6287-6296. 6) Chang BY, Huang MM, Francesco M, et al. The Bruton tyrosine kinase inhibitor PCI-32765 ameliorates autoimmune arthritis by inhibition of multiple effector cells. Arthritis Res Ther. 2011;13(4):R115, page 5 of 6 CMRC-02168-2 12/17. 7) Buggy JJ, Elias L. Bruton tyrosine kinase (BTK) and its role in B-cell malignancy. Int Rev Immunol. 2012;31(2):119-132. 8) Khare A, Viswanathan B, Gund R, et al. Role of Bruton's tyrosine kinase in macrophage apoptosis. Apoptosis. 2011;16(4):334-346. 9) Iwaki S, Tkaczyk C, Satterthwaite AB, et al. BTK plays a crucial role in the amplification of FcεRI-mediated mast cell activation by Kit. J Biol Chem. 2005;280(48):40261-40270.