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PCI-32765 and ITK

Gayathri Natarajan, Cesar Terrazas, Steve Oghumu, Sanjay Varikuti, Jason A Dubovsky, John C Byrd, Abhay R Satoskar
Ibrutinib (PCI-32765) is an irreversible dual Btk/Itk inhibitor shown to be effective in treating several B cell malignancies. However, limited studies have been conducted to study the effect of this drug on myeloid cell function. Hence, we studied the effect of ibrutinib treatment on TLR-4 mediated activation of bone marrow derived dendritic cell culture (DCs). Upon ibrutinib treatment, LPS-treated DCs displayed lower synthesis of TNF-α and nitric oxide (NO) and higher induction of IL-6, TGF-β, IL-10 and IL-18...
2016: Oncoimmunology
Parviz Kokhaei, Farhad Jadidi-Niaragh, Abdolreza Sotoodeh Jahromi, Anders Osterborg, Håkan Mellstedt, Mohammad Hojjat-Farsangi
Targeted therapies have appeared as new treatment options for several disease types, including cancer and autoimmune disorders. Of several targets, tyrosine kinases (TKs) are among the most promising. Overexpression of TKs provides a target for novel therapeutic agents, including small molecule inhibitors of tyrosine kinases (TKI). Ibrutinib (PCI-32765) is a TKI of Bruton's tyrosine kinase (Btk), a key kinase of the B-cell receptor signaling pathway that plays a significant role in the proliferation, differentiation and survival of B cells...
2016: Journal of Drug Targeting
L Vargas, A Hamasy, B F Nore, C I E Smith
BTK and ITK are cytoplasmic tyrosine kinases of crucial importance for B and T cell development, with loss-of-function mutations causing X-linked agammaglobulinemia and susceptibility to severe, frequently lethal, Epstein-Barr virus infection, respectively. Over the last few years, considerable efforts have been made in order to develop small-molecule inhibitors for these kinases to treat lymphocyte malignancies, autoimmunity or allergy/hypersensitivity. The rationale is that even if complete lack of BTK or ITK during development causes severe immunodeficiency, inactivation after birth may result in a less severe phenotype...
August 2013: Scandinavian Journal of Immunology
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