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.
Citation
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. (2018) Highly fluorescent and HDAC6 selective scriptaid analogues. European Journal of Medicinal Chemistry. 162:321-333.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping