Thermal profiling reveals phenylalanine hydroxylase as an off-target of panobinostat

Isabelle Becher, Thilo Werner, Carola Doce, Esther A. Zaal, Ina Tögel, Crystal A. Khan, Anne Rueger, Marcel Muelbaier, Elsa Salzer, Celia R. Berkers, Paul F Fitzpatrick, Marcus Bantscheff, Mikhail M. Savitski

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


We describe a two-dimensional thermal proteome profiling strategy that can be combined with an orthogonal chemoproteomics approach to enable comprehensive target profiling of the marketed histone deacetylase inhibitor panobinostat. The N-hydroxycinnamide moiety is identified as critical for potent and tetrahydrobiopterin-competitive inhibition of phenylalanine hydroxylase leading to increases in phenylalanine and decreases in tyrosine levels. These findings provide a rationale for adverse clinical observations and suggest repurposing of the drug for treatment of tyrosinemia.

Original languageEnglish (US)
Pages (from-to)908-910
Number of pages3
JournalNature Chemical Biology
Issue number11
StatePublished - Nov 1 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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