RuBi-Ruxolitinib: A Photoreleasable Antitumor JAK Inhibitor

J Am Chem Soc. 2024 May 15;146(19):13317-13325. doi: 10.1021/jacs.4c01720. Epub 2024 May 3.

Abstract

We describe the synthesis and biological testing of ruthenium-bipyridine ruxolitinib (RuBiRuxo), a photoreleasable form of ruxolitinib, a JAK inhibitor used as an antitumoral agent in cutaneous T-cell lymphomas (CTCL). This novel caged compound is synthesized efficiently, is stable in aqueous solution at room temperature, and is photoreleased rapidly by visible light. Irradiation of RuBiRuxo reduces cell proliferation and induces apoptosis in a light- and time-dependent manner in a CTCL cell line. This effect is specific and is mediated by a decreased phosphorylation of STAT proteins. Our results demonstrate the potential of ruthenium-based photocompounds and light-based therapeutic approaches for the potential treatment of cutaneous lymphomas and other pathologies.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis* / drug effects
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Humans
  • Janus Kinase Inhibitors / chemical synthesis
  • Janus Kinase Inhibitors / chemistry
  • Janus Kinase Inhibitors / pharmacology
  • Janus Kinases / antagonists & inhibitors
  • Janus Kinases / metabolism
  • Light
  • Molecular Structure
  • Nitriles* / chemical synthesis
  • Nitriles* / chemistry
  • Nitriles* / pharmacology
  • Pyrazoles* / chemical synthesis
  • Pyrazoles* / chemistry
  • Pyrazoles* / pharmacology
  • Pyrimidines* / chemical synthesis
  • Pyrimidines* / chemistry
  • Pyrimidines* / pharmacology
  • Ruthenium / chemistry
  • Ruthenium / pharmacology