YX862

YX862 : Degrader (PROTAC) of HDAC8

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

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Probe YX862 is in the process of SERP review.

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Information

HDAC8

Degrader (PROTAC)

up to 250 nM

In Vitro Validations

Uniprot ID: Q9BY41

Target Class: Epigenetic

Target SubClass: Histone deacetylase

Potency: IC50

Potency Value: 194.7 ± 17.1 nM

Potency Assay: Enzymatic assay

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Histone deacetylase 8, HDACL1, HDAC8, HDAC8_HUMAN, ...

DOI Reference: 10.1021/acs.jmedchem.4c00761

Uniprot ID: Q9BY41

Target Class: Epigenetic

Target SubClass: Histone deacetylase

Potency: Activity

Potency Value: ~ 500 nM

Potency Assay: AlphaLISA assay to measure the ternary complex formation among HDAC8, PROTAC, and the VHL complex (consisting of VHL and elongin B and C)

PDB ID for probe-target interaction (3D structure): --

Target aliases:

Histone deacetylase 8, HDACL1, HDAC8, HDAC8_HUMAN, ...

DOI Reference: 10.1021/acs.jmedchem.4c00761

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay, off target (cells): No HDAC1, 2 or 3 were observed up to 4 uM and 24h incubation.

Potency assay, off target (cells): Proteome-wide target specificity of YX862 was performed using a tandem mass tag (TMT)-based quantitative proteomic profiling in MBA-MD-231 cells. Cells were treated with 100 nM YX862. Over 6000 quantifiable proteins were detected in the proteomic profiling experiment, and no significantly downregulated proteins (FC > 1.5, p-value < 0.001) including HDAC3 and other HDACs were identified. To gain insight into the effect of YX862 on global histone PTMs, an optimized mass spectrometry-based approach to quantify PTM changes (acetylation and methylation) after YX862 treatment was carried out. MDA-MB-231 cells were treated with DMSO or 200 nM YX862 for 6 or 24 h before they were harvested for LC/MS/MS analysis. Overall, no profound PTM upregulation with YX862 treatment was observed.

Potency assay (off target): inhibited HDAC3 with IC50 of 2330 nM

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

This is a potent and selective PROTAC for HDAC8 that can be used to assess the effect of HDAC8 degradation in tissue culture. It is remarkable in displaying hardly any "Hook effect".

(last updated: 20 Feb 2025 )