With RET solvent-front G810C/R/S mutations identified as the major on-target mechanism of acquired resistance to selpercatinib and pralsetinib, efforts are underway to develop RET solvent-front mutant effective TKIs.2,13,14 Previously, we characterized several alkynyl nicotinamide-based, type II RET TKIs for their efficacy in subcutaneous (s.c.)cell-derived xenograft (CDX) models of BaF3/KIF5B-RET(G810C) (B/KR(G810C) tumors.13 Here, we expanded the study to include HSN748, HSND19 and HSND14 in KIF5B-RET oncogene-induced lung tumors in transgenic mice and in B/KR(G810C) brain tumors. The gene discussed is KIF5B; the disease is brain neoplasm.