| Literature DB >> 27669419 |
Isabelle Becher1,2, Thilo Werner1, Carola Doce1, Esther A Zaal3, Ina Tögel1, Crystal A Khan4, Anne Rueger1, Marcel Muelbaier1, Elsa Salzer1, Celia R Berkers3, Paul F Fitzpatrick4, Marcus Bantscheff1, Mikhail M Savitski1,2.
Abstract
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.Entities:
Mesh：
Substances：
Year: 2016 PMID： 27669419 DOI： 10.1038/nchembio.2185
Source DB: PubMed Journal: Nat Chem Biol ISSN： 1552-4450 Impact factor: 15.040