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YX968 | YX968 : Degrader (PROTAC) of HDAC3, HDAC8
RATINGS:
Cellular Use: (4 reviews)

In Model Organisms: (0 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
HDAC3
  • IC50:283.8 ± 50.6 nM
  • DC50:1.7 nM
  • Dmax:95%
HDAC8
  • IC50:740.1 ± 302.7 nM
  • DC50:6.1 nM
  • Dmax:95%
Degrader (PROTAC)
100 nM

Selectivity

In Cell Selectivity Assessment
Potency Assay Off-Target:
Tandem Mass Tag (TMT)-based quantitative proteomic profiling experiment was used to assess selectivi ...
In Vitro Selectivity Assessment
Potency Assay Off-Target:
HDAC1 IC50 591.0 ± 87.5 nM enzymatic assay

Potency
Cellular
In Vitro

HDAC3

Mode of Action: Degrader (PROTAC)

Structure-Activity-Relationship data available? No

DOI Reference: 10.1016/j.chembiol.2023.07.010

HDAC8

Mode of Action: Degrader (PROTAC)

Structure-Activity-Relationship data available? Yes

DOI Reference: 10.1016/j.chembiol.2023.07.010

Negative Control Compounds

CANSAR4199059
Notes: Negative control compound YX968-NC, in which two chiral centres in the VHL binding motif of YX968 were reversed, abolishing binding to VHL, were unable to degrade HDAC3/8

Chemical Information

Molecular Formula C45H66N8O5S
SMILEs CCCNNC(=O)c1ccc(N2CCN(CCCCCCCC(=O)N[C@H](C(=O)N3C[C@H](O)C[C@H]3C(=O)N[C@@H](C)c3ccc(-c4scnc4C)cc3)C(C)(C)C)CC2)cc1
InChI InChI=1S/C45H66N8O5S/c1-7-22-47-50-42(56)35-18-20-36(21-19-35)52-26-24-51(25-27-52)23-12-10-8-9-11-13-39(55)49-41(45(4,5)6)44(58)53-29-37(54)28-38(53)43(57)48-31(2)33-14-16-34(17-15-33)40-32(3)46-30-59-40/h14-21,30-31,37-38,41,47,54H,7-13,22-29H2,1-6H3,(H,48,57)(H,49,55)(H,50,56)/t31-,37+,38-,41+/m0/s1
Molecular weight 830.49 Da
AlogP 0.0
HBond acceptors 13
HBond donors 5
Atoms 125

References

Publications

Cross References

canSAR

Vendors

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Expert Reviews

by SERP
(on 26 Oct 2023 )
Cellular Use Rating
YX968 is a well characterized PROTAC with excellent selectivity for its two targets (HDAC3 and HDAC8), demonstrated with classical Western Blotting techniques as well as unbiased proteomics analysis....
by SERP+
(on 31 Oct 2024 )
Cellular Use Rating
Broader in cell selectivity data and proof of HDAC3 engagement data is needed.
by SERP+
(on 31 Oct 2024 )
Cellular Use Rating
( The reviewer did not leave any comments )
by SERP
(on 20 Feb 2025 )
Cellular Use Rating
A useful probe for interrogating the effect of combined degradation of HDAC3 and -8. It may be worth considering the degradation of the off-targets NCOR1 and EPHX2.
Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria