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Review
. 2014 May;10(6):957-67.
doi: 10.2217/fon.14.51.

Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase

Matthew S Davids  1 , Jennifer R Brown
Affiliations
Review

Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase

Matthew S Davids et al. Future Oncol. 2014 May.

Abstract

Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for B-cell survival and proliferation. In preclinical studies, ibrutinib bound to Bruton's tyrosine kinase with high affinity, leading to inhibition of B-cell receptor signaling, decreased B-cell activation and induction of apoptosis. In clinical studies, ibrutinib has been well-tolerated and has demonstrated profound anti-tumor activity in a variety of hematologic malignancies, most notably chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), leading to US FDA approval for relapsed CLL and MCL. Ongoing studies are evaluating ibrutinib in other types of non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and Waldenström's macrogobulinemia, in larger Phase III studies in CLL and MCL, and in combination studies with monoclonal antibodies and chemotherapy. Future studies will combine ibrutinib with other promising novel agents currently in development in hematologic malignancies.

Keywords: B-cell receptor; BTK; CLL; MCL; NHL; ibrutinib; kinase; lymphocytosis.

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Figures

Figure 1
Figure 1
Chemical structure of ibrutinib (formerly PCI-32765).
Figure 2
Figure 2. B-cell receptor signaling pathway
Ibrutinib targets BTK, a kinase that is critical for signal transduction through the B-cell receptor pathway. BTK: Bruton’s tyrosine kinase; CLL: Chronic lymphocytic leukemia.
See this image and copyright information in PMC

References

    1. de Weers M, Mensink RG, Kraakman ME, Schuurman RK, Hendriks RW. Mutation analysis of the Bruton’s tyrosine kinase gene in X-linked agammaglobulinemia: identification of a mutation which affects the same codon as is altered in immunodeficient xid mice. Hum Mol Genet. 1994;3(1):161–166. - PubMed
    1. Herman SE, 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. - PMC - PubMed
    1. Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32–42. The most definitive published results of ibrutinib in relapsed chronic lymphocytic leukemia. - PMC - PubMed
    1. Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013;369(6):507–516. The most definitive published results of ibrutinib in relapsed mantle cell lymphoma. - PMC - PubMed
    1. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, Phase 3 trial. Lancet. 2010;376(9747):1164–1174. - PubMed

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