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Can I read The Nuclear Export Inhibitor Aminoratjadone is a Potent Effector in Extracellular-Targeted Drug Conjugates on EtoBox?
The Nuclear Export Inhibitor Aminoratjadone is a Potent Effector in Extracellular-Targeted Drug Conjugates by Philipp Klahn; Verena Fetz; Antje Ritter; Wera Collisi; Bettina Hinkelmann; Tatjana Arnold; Werner Tegge; Katharina Rox; Stephan Hüttel; Kathrin I. Mohr; Joachim Wink; Marc Stadler; Josef Wissing; Lothar Jänsch; Mark Brönstrup is a Chemistry article available to read on EtoBox.
What is The Nuclear Export Inhibitor Aminoratjadone is a Potent Effector in Extracellular-Targeted Drug Conjugates about?
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 ( 16-aminoratjadone with IC = 260 pM against MCF-7 cells, or 19-oxoratjadone with IC = 100 pM against A-549 cells). Mechanistically, the conjugates retained a nuclear export inhibitory activity through binding CRM1. To demonstrate a proof-of-principle for cellular targeting, folate- and luteinizing hormone releasing hormone (LHRH)-based carrier molecules were synthesized and coupled to aminoratjadones as well as fluorescein for cellular efficacy and imaging studies, respectively. The Trojan-Horse conjugates selectively addressed receptor-positive cell lines and were high
Who reads The Nuclear Export Inhibitor Aminoratjadone is a Potent Effector in Extracellular-Targeted Drug Conjugates?
It is typically read by researchers, students, and practitioners in Chemistry.
- Author
- Philipp Klahn; Verena Fetz; Antje Ritter; Wera Collisi; Bettina Hinkelmann; Tatjana Arnold; Werner Tegge; Katharina Rox; Stephan Hüttel; Kathrin I. Mohr; Joachim Wink; Marc Stadler; Josef Wissing; Lothar Jänsch; Mark Brönstrup
- Publisher
- The Royal Society of Chemistry; Royal Society of Chemistry; Royal Society of Chemistry (RSC) (ISSN 2041-6520)
- Published
- 2019
- Language
- EN
- Field
- Chemistry (Physical Sciences)