RO4929097

溶解度:Unknown

储存条件:at -20℃ 2 years

生物活性

PCI-32765 is a high potent irreversible BTK inhibitor with an IC50 of 0.46 nM for the purified Btk.^[1]PCI-32765 is highly active and well tolerated in CLL/SLL pts irrespective of high risk genomic abnormalities. Although follow-up is short, the high response rate and very low progression rate suggests that PCI-32765 may be an important new targeted treatment approach for CLL pts. In ex vivo assays with whole bold, PCI-32765 prevents the activation of human BCR with an IC50 of about 0.2 μM, while not influencing the activation of T cell. Treatment of CD40 or BCR activated CLL cells with PCI-32765 results in inhibition of BTK tyrosine phosphorylation and also effectively abrogates downstream survival pathways activated by this kinase including ERK1/2, PI3K, and NF-κB. In addition, PCI-32765 prevents activation-induced proliferation of CLL cells in vitro, and effectively inhibits survival signals provided externally to CLL cells from the microenvironment including soluble factors (CD40L, BAFF, IL-6, IL-4, and TNF-α), fibronectin engagement, and stromal cell contact.^[2] PCI-32765 is originally developed by Pharmacyclics. And participants is been invited for the phase I clinical trials.

参考文献

[1] Chang BY et al. Arthritis Res Ther. 2011 Jul 13;13(4):R115.

[2] Herman SE et al. Blood. 2011 Jun 9;117(23):6287-96.