Uses
ONO-4059 hydrochloride is a potent orally active BTK (Bruton's tyrosine kinase) inhibitor, IC50: 2.2nM.It is a potent and orally active Bruton agammaglobulinemia tyrosine kinase (BTK) in hibitor. Upon administration,it covalently binds to BTK within B cells,thereby preventing B-cell receptor signaling and impeding B-cell development.
Biological Activity
Tirabrutinib Hydrochloride (ONO-4059, GS-4059) is a highly potent and selective BTK inhibitor with IC50 of 2.2 nM.
in vitro
Compared with Lck, Fyn, LynA, ONO-4059 is more selective for BTK, and only inhibits anti-IgM-induced B cell activation in a concentration-dependent manner, but not anti-CD3/CD28-induced Activation of human PBMCs to T lymphocytes. ONO/GS-4059 inhibited cell proliferation in some malignant B cells, but also in the nanomolar concentration range, induced the classical apoptotic response of TMD8 cells.
in vivo
In the CIA mouse model, ONO-4059 exerted its curative effect by inhibiting the production of inflammatory chemokines and cytokines such as IL-6, IL-8, TNFalpha, etc. in monocytes, accompanied by cartilage erosion, bone damage, vascular Recession of nebula formation. In preclinical animal models and clinical CLL and NHL patients, ONO-4059 has antitumor activity, good safety and long-lasting efficacy.
