Brigatinib NEW

Bugitinib is a tyrosine kinase receptor (MERTK) inhibitor that can be used in combination with epidermal growth factor receptor (EGFR) inhibitors for cancer treatment.

Pharmacological action

Bouguer for, is a tyrosine kinase inhibitor in vitro and clinical can reach concentrations, for a variety of kinases, including ALK, ROS1 proto-oncogene (C - rosproto - oncogene1), insulin-like growth factor 1 receptor (insulin - likegrowthfactor1receptor, IGF-1R and FMS-like tyrosinekinase 3(FMS-liketyrosine kinase, FLT-3), as well as epidermal growth factor receptor (EGFR) deletion and point mutation have inhibitory activity. In vitro and in vivo, bugitinib inhibited the phosphorylation of ALK itself and mediated the phosphorylation of downstream signaling proteins STAT3, AKT, ERK1/2 and S6. Bugitinib also inhibited the proliferation of cell lines expressing EML4-ALK and NFM-ALK fusion proteins in vitro, and showed dose-dependent effects in inhibiting the growth of EML4-ALK+NSCLC xenografts in mice. In clinical practice, with a concentration of ≤500nmol•L-1, bugitinib can inhibit the survival rate of EML4-ALK cells and 17 mutants in vitro, which are associated with resistance to ALK inhibitors. Including crizotinib and EGFR-Del(E746-A750), ROS1-L2026M, FLT3-F691L and FLT3-D835Y. Bugtinib also showed antitumor activity in vivo against four EML4-ALK mutants, including G1202R and L1196M mutants isolated from plasma in patients with advanced NSCLC after crizotinib treatment. Bugitinib can reduce the load of intracranial implanted ALK with tumor driving cell lines and prolong the survival of mice.