Ibrutinib | BTK inhibitor

Ibrutinib (936563-96-1) is a very potent (IC₅₀ = 0.5nM) irreversible inhibitor of Bruton tyrosine kinase (BTK) that blocks activation of the B-cell antigen receptor (BCR).¹ Ibrutinib also potently inhibits several other kinases including BLK, BMS, FGR, EGFR, and ITK.  It is a clinically useful drug to treat B cell cancers. It inhibits CLL cell migration and survival^2,3 and downregulates expression of CD20⁴.  It enhanced antitumor immune responses in combination with anti PD-L1 blockade via its inhibition of ITK (IL2-inducible T-cell kinase).⁵

References/Citations:

1) Honigberg et al. (2010), 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
2) Ponader et al. (2012), The Bruton tyrosine kinase Inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo; Blood 119 1182
3) De Rooij et al. (2012), The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia; Blood 119 2590
4) Pavlasoca et al. (2016), Ibrutinib inhibits CD20 upregulation on CLL B cells mediated by the CXCR4/SDF-1 axis; Blood 128 1609
5) Sagiv-Barfi et al. (2015), Therapeutic antitumor immunity by checkpoint blockade is enhanced by ibrutinib, an inhibitor of both BTK and ITK; Proc. Natl. Acad. Sci. USA 112 E966
6) Weber et al. (2017), Bruton’s Tyrosine Kinase: An Emerging Key Player in Innate Immunity, Front. Immunol. 8 1454