PUBLICATION

Highly fluorescent and HDAC6 selective scriptaid analogues

Authors
Fleming, C.L., Natoli, A., Schreuders, J., Devlin, M., Yoganantharajah, P., Gibert, Y., Leslie, K.G., New, E.J., Ashton, T.D., Pfeffer, F.M.
ID
ZDB-PUB-181119-5
Date
2018
Source
European Journal of Medicinal Chemistry   162: 321-333 (Journal)
Registered Authors
Gibert, Yann
Keywords
4MS, Fluorescence, HDAC, Imaging, Naphthalimide, Scriptaid, Zebrafish
MeSH Terms
  • Animals
  • Blood Vessels/diagnostic imaging
  • Blood Vessels/metabolism
  • Cytoplasm/metabolism
  • Diagnostic Imaging/methods
  • Fluorescence
  • Histone Deacetylase 6/antagonists & inhibitors*
  • Histone Deacetylase Inhibitors/pharmacokinetics
  • Histone Deacetylase Inhibitors/therapeutic use
  • Hydroxylamines/chemical synthesis
  • Hydroxylamines/chemistry*
  • Hydroxylamines/pharmacokinetics
  • Quinolines/chemical synthesis
  • Quinolines/chemistry*
  • Quinolines/pharmacokinetics
  • Zebrafish/metabolism
PubMed
30448419 Full text @ Eur. J. Med. Chem.
Abstract
Fluorescent scriptaid analogues with excellent HDAC6 selectivity (HDAC1/6 > 500) and potency (HDAC6 IC50 < 5 nM) have been synthesised and evaluated. The highly fluorescent nature of the compounds (up to ΦF = 0.83 in DMSO and 0.38 in aqueous buffer) makes them ideally suited for cellular imaging and visualisation of their cytoplasmic localisation was readily accomplished. Whole organism imaging in zebrafish confirmed both the vascular localisation of the new inhibitors and the impact of HDAC6 inhibition on in vivo development.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping