Histone deacetylase 6 (HDAC6) catalyzes the removal of an acetyl group from lysine residues of several non-histone proteins. Here we report the preparation of thiazole-, oxazole- and oxadiazole-containing biaryl hydroxamic acids by a short synthetic procedure. We identified them as selective HDAC6 inhibitors by investigating the inhibition of recombinant HDAC enzymes and the protein acetylation in cells by western blotting (tubulin vs. histone acetylation). The most active compounds exhibited nanomolar potency and high selectivity for HDAC6. For example an oxazole hydroxamate inhibits HDAC6 with an IC50 of 59 nM and has a selectivity index of >200 against HDAC1 and HDAC8. This is the first report showing that the nature of a heterocycle directly connected to a zinc binding group (ZBG) can be used to modulate subtype selectivity and potency for HDAC6 inhibitors to such an extent. We rationalize the high potency and selectivity of the oxazoles by molecular modelling and docking.
Pharmacology, Toxicology and Pharmaceutical Science
16
16%
Biochemistry, Genetics and Molecular Biology
6
6%
Medicine and Dentistry
6
6%
Agricultural and Biological Sciences
3
3%
Other
4
4%
Unknown
31
32%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 January 2026.
All research outputs
#3,143,243
of 24,652,007 outputs
Outputs from Journal of Medicinal Chemistry
#3,026
of 22,847 outputs
Outputs of similar age
#51,895
of 400,952 outputs
Outputs of similar age from Journal of Medicinal Chemistry
#29
of 151 outputs
Altmetric has tracked 24,652,007 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 22,847 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.9. This one has done well, scoring higher than 86% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 400,952 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 151 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 80% of its contemporaries.
