Mechanism of Action (MOA)

In preclinical studies, pralsetinib was designed for potent and selective inhibition of RET1,27

In cellular assays, pralsetinib inhibited RET at approximately 14-, 40-, and 12-fold lower concentrations than VEGFR2, FGFR2, and JAK2, respectively.


Pralsetinib exhibited anti-tumor activity in cultured cells and animal tumor implantation models harboring oncogenic RET fusions or mutations, including KIF5B-RET, CCDC6-RET, RET M918T, RET C634W, RET V804E, RET V804L, and RET V804M.

tumor growth

Pralsetinib prolonged survival in mice implanted intracranially with tumor models expressing KIF5B-RET or CCDC6-RET.

ATP=adenosine triphosphate; FGFR2=fibroblast growth factor receptor 2; JAK2=Janus kinase 2; RET=rearranged during transfection; VEGFR2=vascular endothelial growth factor receptor 2.