Small Molecule Ligands
for Active Targeting of TrkC-Expressing Tumor Cells
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Abstract
A small molecule motif was used in “active targeting”
to deliver cytotoxic substances into tumor cells that express the
TrkC receptor. Underlying this study was the hypothesis that internalization
of targeted conjugates into cells would be facile if mediated by receptor
binding and receptor–ligand internalization. Initial experiments
using 6-mercaptopurine gave encouraging data but demonstrated the
importance of maintaining solubility and high cytotoxicity. Conjugates
of the targeting agent with a cytotoxic rosamine (similar to a rhodamine)
were more successful. Targeting of TrkC was observed, validated in
a series of competition experiments featuring other TrkC ligands,
and accumulation into lysosomes was observed, as expected for receptor-mediated
internalization
