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Drug intelligence / Profile preview
pralsetinib + selpercatinib
- Development stage
- Unknown
- Lead developer
- Eli Lilly
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Pralsetinib and selpercatinib are selective RET tyrosine kinase inhibitors (TKIs) used to treat patients with RET gene alterations, particularly in non-small cell lung cancer (NSCLC) and thyroid cancer. Both drugs received FDA accelerated approval in 2020 based on the pivotal ARROW trial (pralsetinib) and LIBRETTO-001 trial (selpercatinib). They work by selectively inhibiting RET by competing with ATP for binding at the adenosine triphosphate-binding site, preventing RET phosphorylation and downstream signaling. Both drugs have demonstrated efficacy against brain metastases and share similar mechanisms of action, though with different safety profiles.
02
Targets
DDR1 (Discoidin domain receptor 1)FGFR1 (Fibroblast growth factor receptor 1)FGFR2 (Keratinocyte growth factor receptor)FGFR3 (Fibroblast growth factor receptor 3)FLT3 (Fms related receptor tyrosine kinase 3)JAK1 (Janus kinase 1)JAK2 (Janus kinase 2)PDGFRB (Platelet-derived growth factor receptor beta)RET (Rearranged during transfection receptor tyrosine kinase)NTRK1 (Tropomyosin-related receptor kinase A)NTRK3 (Tropomyosin receptor kinase C)VEGFR-1 (Vascular endothelial growth factor receptor 1)VEGFR2 (Vascular endothelial growth factor receptor 2)VEGFR4 (Vascular endothelial growth factor Receptor-3)
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