Open AccessSmall Molecule Ligands for Active Targeting of TrkC-Expressing Tumor Cells
Author(s) -
Eunhwa Ko,
Anyanee Kamkaew,
Kevin Burgess
Publication year - 2012
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml300227d
Subject(s) - internalization , tropomyosin receptor kinase c , small molecule , cytotoxicity , receptor , conjugate , ligand (biochemistry) , cytotoxic t cell , microbiology and biotechnology , chemistry , cancer research , biochemistry , biology , in vitro , mathematical analysis , platelet derived growth factor receptor , mathematics , growth factor
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.