CZH-Z16

CZH-Z16 : Degrader (PROTAC) of HDAC8

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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Probe CZH-Z16 is in the process of SERP review.

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Information

HDAC8

Degrader (PROTAC)

100 nM

Probe Availability:

MedKoo

In Vitro Validations

No in Vitro Validations

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Selectivity within family: Z16 shows very little inhibitory activity agains the HDAC family HDAC1 IC50 1.7 ± 0.3 uM, HDAC2 IC50 20.1 ± 4.6 um, HDAC3 IC50 1.2 ± 0.2 uM, HDAC8 IC50 2.7 ± 0.9 uM).

Potency assay, off target (cells): No obvious HDAC1, HDAC2, HDAC3, HDAC4, HDAC6, HDAC7, and HDAC11 degradation was observed on Western blot upon Z16 treatment, thus indicating good selectivity among HDAC isoenzymes. Additionally, Z16 did not significantly affect the intracellular levels of IKZF1, IKZF3, and GSPT1 in Jurkat cells, which are the neo-substrates of CRBN.

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

The cellular effects on biological pathways is ~3logs weaker than the degradation effects in the same cells. No proteomics data (and few other data) are supplied to show that the cell biology is only derived from target protein degradation. Until additional characterization of the key compounds' effects on proteins other than HDAC8 are available, the compound should be used with caution in experiments further describing effects that could be due to off targets.

(last updated: 6 Nov 2024 )

SERP Ratings

In Cell Rating

SERP Comments:

This compound is among the most potent HDAC8 degraders currently available. A limitation for full recommendation as a cellular probe for HDAC8 is the current lack of global proteomics data to confirm selectivity for HDAC8 degradation in an unbiased manner.

(last updated: 25 Nov 2024 )