Ibrutinib, also known as PCI-32765, is a selective and irreversible inhibitor of the enzyme Brutons tyrosine kinase (BTK). It inhibited BTK potently, with an IC50 of 0.72 nM in enzymology assays and with an IC50 of 10 nM in cellular assay with Ramos cells. It demonstrated preference toward BTK over closely related kinases, blocked B cell function and BTK-dependent processes, and demonstrated clear efficacy in a mouse arthritis model. Young P.R., et al. "Discovery of selective irreversible inhibitors for Brutons tyrosine kinase." ChemMedChem. 2: 58-61 (2007).
Ibrutinib blocked B-cell antigen receptor (BCR) signaling in human peripheral B cells at concentrations which did not change T cell receptor signaling, reduced the level of circulating autoantibodies and completely suppressed collagen-induced arthritis in mice, inhibited the production of autoantibodies and the development of kidney disease in the MRL-Fas(lpr) lupus model, and induced objective clinical responses in dogs with spontaneous B-cell non-Hodgkin lymphoma. Active site occupancy of BTK was closely correlated with the inhibition of BCR signaling and in vivo efficacy. Honigberg L.A., 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. USA 107: 13075-13080 (2010).
Ibrutinib was well tolerated and had significant activity in patients with relapsed/refractory B-cell malignancies. Advani R.H., et al. "Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies." J. Clin. Oncol. 31: 88-94 (2013).
Ibrutinib is the active ingredient in the drug product sold under the trade name Imbruvica®. This drug is currently approved in at least one country for use in patients with mantle cell lymphoma and chronic lymphocytic leukemia. NOTE: THE IBRUTINIB, FREE BASE RESEARCH COMPOUND SOLD BY LC LABORATORIES IS NOT IMBRUVICA®, AND IS NOT FOR HUMAN USE.
Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use
This product is offered for R&D use in accordance with (i) 35 USC 271(e)+A13(1) in the U.S.; (ii) Section 69.1 of Japanese Patent Law in Japan; (iii) Section 11, No. 2 of the German Patent Act of 1981 in Germany; (iv) Section 60, Paragraph 5b of the U.K. Patents Act of 1977 in the U.K.; (v) Sections 55.2(1) and 55.2(6) and other common law exemptions of Canadian patent law; (vi) Section 68B of the Patents Act of 1953 in New Zealand together with the amendment of same by the Statutes Amendment Bill of 2002; (vii) such related legislation and/or case law as may be or become applicable in the aforementioned countries; and (viii) such similar laws and rules as may apply in various other countries.
Not available in some countries; not available to some institutions; not available for some uses.
Related Terms:
[Imbruvica] M.W. 440.50 C25H24N6O2 [936563-96-1]
Solubility
Soluble in DMSO at 200 mg/mL; soluble in ethanol at 25 mg/mL with slight warming
