Ibrutinib-d5 is intended for use as an internal standard for the quantification of ibrutinib by GC- or LC-MS. Ibrutinib is an irreversible inhibitor of Bruton’s tyrosine kinase (BTK; IC50 = 0.5 nM) that selectively blocks B cell activation, promoting apoptosis and preventing homing to the protective tumor microenvironment, at concentrations that do not affect T cell receptor signaling (1,000-fold more potent).1,2 It has been reported to inhibit autophosphorylation of BTK (IC50 = 11 nM), phosphorylation of PLCγ (IC50 = 29 nM), a substrate of BTK, and phosphorylation of ERK (IC50 = 13 nM), a further downstream kinase.1 Formulations containing it have been examined clinically for the treatment of diseases associated with B cell antigen receptor signaling, including mantle cell lymphoma, chronic lymphocytic leukemia, and non-Hodgkin lymphoma.3,1,4
1.Honigberg, L.A., Smith, A.M., 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 malignancyProc. Natl. Acad. Sci. USA107(29)13075-13080(2010) 2.Herman, S.E.M., Gordon, A.L., Hertlein, E., et al.Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765Blood117(23)6287-6296(2011) 3.Leslie, L.A., and Younes, A.Targeting oncogenic and epigenetic survival pathways in lymphomaLeuk. Lymphoma.54(11)2365-2376(2013) 4.Wu, M., Akinleye, A., and Zhu, X.Novel agents for chronic lymphocytic leukemiaJ. Hematol. Oncol.636(2013)