[CAS NO. 1197953-54-0]  Brigatinib

Brigatinib potently inhibits the in vitro kinase activity of ALK (IC ₅₀ , 0.6 nM) and all five mutant variants tested, including G1202R (IC ₅₀ , 0.6-6.6 nM). Brigatinib demonstrates a high degree of selectivity, only inhibiting 11 additional native or mutant kinases with IC ₅₀ <10 nM. These include ROS1, FLT3, and mutant variants of FLT3 (D835Y) and EGFR (L858R; IC ₅₀ , 1.5-2.1 nM). Brigatinib exhibits more modest activity against EGFR with a T790M resistance mutation (L858R/T790M), native EGFR, IGF1R, and INSR (IC ₅₀ , 29-160 nM) and does not inhibit MET (IC ₅₀ >1000 nM). In cellular assays, brigatinib inhibits ALK and ROS1 with IC ₅₀ s of 14 and 18 nM, respectively. Brigatinib inhibits FLT3 and IGF-1R with about 11-fold lower potency (IC ₅₀ , 148-158 nM) and inhibits mutant variants of FLT3 and EGFR with 15- to 35-fold lower potency (IC ₅₀ , 211-489 nM). Brigatinib inhibits cell growth with GI ₅₀ values ranging from 503 to 2,387 nM in three ALK-negative ALCL and NSCLC cell lines ^[1] . Brigatinib inhibits ALK activity and abrogates proliferation of ALK addicted neuroblastoma cell lines, with IC ₅₀ of 75.27 ± 8.89 nM. Brigatinib inhibits both the ALK-I1171N and the ALK-G1269A mutant receptors at 10 and 4 nM levels, respectively ^[3] .

MCE has not independently confirmed the accuracy of these methods. They are for reference only.