The nuclear export inhibitor aminoratjadone is a potent effector in extracellular-targeted drug conjugates.

ABSTRACT: The concept of targeted drug conjugates has been successfully translated to clinical practice in oncology. Whereas the majority of cytotoxic effectors in drug conjugates are directed against either DNA or tubulin, our study aimed to validate nuclear export inhibition as a novel effector principle in drug conjugates. For this purpose, a semisynthetic route starting from the natural product ratjadone A, a potent nuclear export inhibitor, has been developed. The biological evaluation of ratjadones functionalized at the 16-position revealed that oxo- and amino-analogues had very high potencies against cancer cell lines (e.g. 16R-aminoratjadone 16 with IC₅₀ = 260 pM against MCF-7 cells, or 19-oxoratjadone 14 with IC₅₀ = 100 pM against A-549 cell

SUBMITTER: Klahn P 

PROVIDER: S-EPMC6540907 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature