651768-07-9Relevant academic research and scientific papers
The effect of various zinc binding groups on inhibition of histone deacetylases 1-11
Madsen, Andreas S.,Kristensen, Helle M. E.,Lanz, Gyrithe,Olsen, Christian A.
, p. 614 - 626 (2014)
Histone deacetylases (HDACs) have the ability to cleave the acetyl groups of ε-N-acetylated lysine residues in a variety of proteins. Given that human cells contain thousands of different acetylated lysine residues, HDACS may regulate a wide variety of processes including some implicated in conditions such as cancer and neurodegenerative disorders. Herein we report the synthesis and ina vitro biochemical profiling of a series of compounds, including known inhibitors as well as novel chemotypes, that incorporate putative new zinc binding domains. By evaluating the compound collection against all 11 recombinant human HDACs, we found that the trifluoromethyl ketone functionality provides potent inhibition of all four subclasses of the Zn2+- dependent HDACs. Potent inhibition was observed with two different scaffolds, demonstrating the efficiency of the trifluoromethyl ketone moiety as a zinc binding motif. Interestingly, we also identified silanediol as a zinc binding group with potential for future development of non-hydroxamate classa I and classa IIb HDAC inhibitors.
Novel histone deacetylase inhibitors: Design, synthesis, enzyme inhibition, and binding mode study of SAHA-Based non-hydroxamates
Suzuki, Takayoshi,Nagano, Yuki,Matsuura, Azusa,Kohara, Arihiro,Ninomiya, Shin-Ichi,Kohda, Kohfuku,Miyata, Naoki
, p. 4321 - 4326 (2007/10/03)
In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) were designed and synthesized as (i) substrate (acetyl lysine) analogues (compounds 3-7), (ii) analogu
