CHMFL-BMX-078

CHMFL-BMX-078 is a highly potent and selective type II irreversible BMX kinase inhibitor with an IC₅₀ of 11 nM. IC50 & Target: IC50: 11 nM (BMX)^[1] In Vitro: Bone marrow kinase in the X chromosome (BMX, also called ETK) is a nonreceptor tyrosine kinase involved in tumorigenicity, cell motility, adhesion, angiogenesis, proliferation, and differentiation. CHMFL-BMX-078 exhibits an IC₅₀ of 11 nM by formation of a covalent bond with cysteine 496 residue in the DFG-out inactive conformation of BMX. It displays a high selectivity profile against the 468 kinases/mutants in the KINOMEscan evaluation and achieves at least 40-fold selectivity over BTK kinase (IC₅₀=437 nM). For inactive state of BMX kinase, CHMFL-BMX-078 displays a binding K_d of 81 nM, while for the active state of BMX kinase, it exhibits a binding K_d of 10200 nM. CHMFL-BMX-078 exhibits antiproliferative effects against BaF3-TEL-BMX cells (GI₅₀=0.016 μM) and selectivity over parental BaF3 cells. CHMFL-BMX-078 is about 80-fold more potent against BMX wt (EC₅₀=5.8 nM) than C496S mutant (EC₅₀=459 nM) for the inhibition of BMX total tyrosine phosphorylation. CHMFL-BMX-078 would serve as a useful pharmacological tool to elucidate the detailed mechanism of BMX mediated signaling pathways^[1]. In Vivo: CHMFL-BMX-078 exhibits a short half-life (T_1/2=0.80 h) in iv injection. CHMFL-BMX-078 also displays an acceptable C_max (13565.23 ng/mL) and AUC_0-t (1386.41 ng/mL h) in iv injection. However, it is not absorbed by oral administration, indicating that this compound could be administrated through iv or ip injection when used as a research tool^[1].