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]
Technical information:
| Chemical Formula: | C25H24N6O2 | |
| CAS #: | 936563-96-1 | |
| Molecular Weight: | 440.5 | |
| Purity: | >99% | |
| Appearance: | White | |
| Chemical Name: | (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one | |
| Solubility: | Up to 100 mM in DMSO | |
| Synonyms: | Ibrutinib, PCI-32765, PCI 32765, PCI32765, CRA-032765 |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage condition: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | Honigberg 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. 2010, 107(29), 13075-13080. Pubmed ID: 20615965 |
| 2. | Herman 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, 6287-6296. Pubmed ID: 21422473 |
| 3. | Chang 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. Pubmed ID: 21752263 |
Other Information:
Product Specification (pdf)
MSDS (pdf)
Certificate of Analysis is available upon request.
