XMU-MP-5 is a new-generation potent and selective ALK inhibitor (IC50=4.15 nM) to overcome crizotinib resistance mutations, including L1196M and G1202R;
XMU-MP-5 significantly induced apoptosis in EML4-ALK Ba/F3 cells did not affect apoptosis in wild-type Ba/F3 cells.
XMU-MP-5 shows highest binding affinities for ALK and its mutants ALK(C1156Y) and ALK(L1196M), with K d values of 0.57, 0.4, and 0.77 nM, respectively.
XMU-MP-5 blocks ALK signaling pathways and inhibits the proliferation of cells harboring either wild-type or mutant EML4-ALK in vitro and suppresses tumor growth in xenograft mouse models in vivo.
XMU-MP-5 induces significant regression of lung tumors in two genetically engineered mouse (GEM) models.
