Summary of affinity data for tested KDAC8 inhibitors
Inhibitor
IC50 (µmol/L)
Continuous assay
IC50 (µmol/L)
Two-step assay
SC50 (µmol/L)
Stabilization curves
ΔTm (°C)
Inhibition mode
TSA
0.70 ± 0.16
0.30 ± 0.07
0.50 ± 0.11
11.96 ± 0.06
Fast reversible binding
SAHA
3.6 ± 0.9
1.9 ± 0.3
3.2 ± 0.9
8.50 ± 0.06
Fast reversible binding
BW164
17 ± 4
4.2 ± 0.6
31 ± 15
7.17 ± 0.06
Fast reversible binding
SATFMK
0.021 ± 0.005
0.021 ± 0.004
-
16.85 ± 0.18
Slow reversible binding (induced fit)
TJ-19-29
0.030 ± 0.009
0.12 ± 0.04
-
4.4 ± 0.3
Covalent inactivation
NEM
0.32 ± 0.09
0.78 ± 0.18
-
4.58 ± 0.26
Covalent inactivation
SC50 is the concentration of half-maximal KDAC8 stabilization and ΔTm indicates the thermal stabilization of KDAC8 in the presence of 100 µmol/L inhibitor. SC50: ligand concentration, with half-maximal stabilization of enzyme activity; -: none
MS: Resources, Investigation, Writing—original draft. AA: Investigation. FJMA: Conceptualization, Formal analysis, Funding acquisition, Supervision, Writing—review & editing. All authors approved the submitted version of the manuscript.
Conflicts of interest
The authors declare that they have no conflicts of interest.
Ethical approval
Not applicable.
Consent to participate
Not applicable.
Consent to publication
Not applicable.
Availability of data and materials
All experimental information is contained in the manuscript and supporting information.
Funding
This research was supported by the LOEWE priority program TRABITA, State of Hesse, Germany. The funder supports the publication of all results from basic research and had no role in the study design and analysis or interpretation of the data.
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