Discovery of 7-(1-methyl-1H-pyrazol-4-yl)-1,6-naphthyridine Derivatives as Potent Inhibitors of Rearranged During Transfection (RET) and RET Solvent-Front Mutants for Overcoming Selpercatinib Resistance

Rearranged during transfection kinase (RET) inhibition has been considered a promising therapeutic approach for treatment of a variety of cancers. However, the clinical therapeutic benefits of the second-generation RET inhibitor selpercatinib are greatly compromised by acquired resistance mediated by solvent-front mutations (e.g., RET