Photoactivatable prodrugs of antimelanoma agent Vemurafenib

Rebecca Horbert, Boris Pinchuk, Paul Davies, Dario Alessi, Christian Peifer (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)
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In this study, we report on novel photoactivatable caged prodrugs of vemurafenib. This kinase inhibitor was the first approved drug for the personalized treatment of BRAF-mutated melanoma and showed impressive results in clinical studies. However, the occurrence of severe side effects and drug resistance illustrates the urgent need for innovative therapeutic approaches. To conquer these limitations, we implemented photoremovable protecting groups into vemurafenib. In general, this caging concept provides spatial and temporal control over the activation of molecules triggered by ultraviolet light. Thus, higher inhibitor concentrations in tumor tissues might be reached with less systemic effects. Our study describes the first development of caged vemurafenib prodrugs useful as pharmacological tools. We investigated their photochemical characteristics and photoactivation. In vitro evaluation proved the intended loss-of-function and the light-dependent recovery of efficacy in kinase and cellular assays. The reported vemurafenib photo prodrugs represent a powerful biological tool for novel pharmacological approaches in cancer research.

Original languageEnglish
Pages (from-to)2099-2107
Number of pages9
JournalACS Chemical Biology
Issue number9
Early online date10 Jun 2015
Publication statusPublished - 18 Sept 2015


  • Cell line, Tumor
  • Cell proliferation
  • Drug resistance, Neoplasm
  • Humans
  • Indoles
  • Melanoma
  • Models, Molecular
  • Photosensitizing agents
  • Prodrugs
  • Protein kinase inhibitors
  • Proto-oncogene proteins B-raf
  • Sulfonamides
  • Journal article
  • Research support, Non-U.S. Gov't


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