Selpercatinib’s target

Selpercatinib is a kinase inhibitor that inhibits wild-type RET and multiple mutant RET isoforms as well as VEGFR1 and VEGFR3, with IC50 values ranging from 0.92nM to 67.8nM. In other enzyme assays, sepatinib also inhibited FGFR 1, 2, and 3 at higher clinically achievable concentrations. In cellular assays, serpatinib inhibited RET at concentrations approximately 60-fold lower than FGFR1 and 2 and approximately 8-fold lower than VEGFR3. Certain point mutations in RET or chromosomal rearrangements involving in-frame fusion of RET with various partners can lead to constitutively activated chimeric RET fusion proteins that can act as oncogenic drivers by promoting cell proliferation in tumor cell lines.