DKFZ-748

DKFZ-748 : Inhibitor of HDAC10

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(0 ratings)

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.

Probe DKFZ-748 is in the process of SERP review.

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Information

HDAC10

Inhibitor

1 µM up to 10 uM
Reviewer recommended concentration: 1 to 5 µM

In Vitro Validations

Uniprot ID: Q969S8

Target Class: Enzyme

Target SubClass: Deacetylase

Potency: IC50

Potency Value: 5 nM

Potency Assay: TR-FRET ligand displacement assay

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

Target aliases:

Polyamine deacetylase HDAC10, HDAC10, HDA10_HUMAN, ...

DOI Reference: 10.1021/jacs.2c05030

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Off Target: HDAC1

Potency end-point : IC50 13 uM

Potency assay (off target): HDAC enzymatic assay (HDAC-glo assay)

Probe Selectivity in Vitro:

2500-fold selectivity factor

Off Target: HDAC2

Potency end-point : IC50 51 uM

Potency assay (off target): HDAC enzymatic assay (HDAC-glo assay)

Probe Selectivity in Vitro:

10000-fold selectivity factor

Off Target: HDAC3

Potency end-point : IC50 <100 uM

Potency assay (off target): HDAC enzymatic assay (HDAC-glo assay)

Probe Selectivity in Vitro:

>10000-fold selectivity factor

Off Target: HDAC6

Potency end-point : IC50 3 uM

Potency assay (off target): HDAC enzymatic assay (HDAC-glo assay)

Probe Selectivity in Vitro:

630-fold selectivity factor

Off Target: HDAC8

Potency end-point : IC50 1.3 uM

Potency assay (off target): HDAC enzymatic assay (HDAC-glo assay)

Probe Selectivity in Vitro:

263-fold selectivity

Off Target: HDAC1

Potency in cells, off target : Kd apparent <100 uM

Potency assay, off target (cells): Proteomic profiling

Probe Selectivity in Cell:

>630-fold selectivity

Off Target: HDAC2

Potency in cells, off target : Kd apparent <100 uM

Potency assay, off target (cells): Proteomic profiling

Probe Selectivity in Cell:

>630-fold selectivity

Off Target: HDAC5

Potency in cells, off target : Kd apparent >100 uM

Potency assay, off target (cells): Proteomic profiling

Probe Selectivity in Cell:

>630-fold selectivity

Off Target: HDAC6

Potency in cells, off target : Kd apparent >100 uM

Potency assay, off target (cells): Proteomic profiling

Probe Selectivity in Cell:

>630-fold selectivity

Off Target: HDAC8

Potency in cells, off target : Kd apparent >100 uM

Potency assay, off target (cells): Proteomic profiling

Probe Selectivity in Cell:

>630-fold selectivity

Off Target: ISOC1

Potency in cells, off target : Kd apparent 40 uM

Potency assay, off target (cells): Proteomic profiling

Probe Selectivity in Cell:

250-fold selectivity

Off Target: ISOC2

Potency in cells, off target : Kd apparent 11 uM

Potency assay, off target (cells): Proteomic profiling

Probe Selectivity in Cell:

79-fold selectivity

Off Target: ALDH1B1

Potency in cells, off target : Kd apparent >100 uM

Potency assay, off target (cells): Proteomic profiling

Probe Selectivity in Cell:

>630-fold selectivity

Off Target: ALDH2

Potency in cells, off target : Kd apparent >100 uM

Potency assay, off target (cells): Proteomic profiling

Probe Selectivity in Cell:

>630-fold selectivity

Off Target: GATD3

Potency in cells, off target : Kd apparent >100 uM

Potency assay, off target (cells): Proteomic profiling

Probe Selectivity in Cell:

>630-fold selectivity

Off Target: MBLAC2

Potency in cells, off target : Kd apparent >100 uM

Potency assay, off target (cells): Proteomic profiling

Probe Selectivity in Cell:

>630-fold selectivity

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SERP ratings and comments

SERP Ratings

In Cell Rating

SERP Comments:

This is an welcome advance in HDAC-specific probes. The original report provides significant SAR data to establish the potency and selectivity of this probe. In general, I would recommend starting off with probe concentrations between 1 to 5 uM for this compound. The optimal concentration may vary depending on the experimental system (cell line, complete media formulation, time point, readout, etc.), and as with any chemical probe, the user should verify by experiment target engagement and lack of off-target effects in their specific experimental system.

(last updated: 14 Apr 2024 )

SERP Ratings

In Cell Rating

SERP Comments:

This probe shows superb potency for HDAC10 as well as excellent selectivity for other members of the HDAC family and non-HDAC metalloproteases. This selectivity extends to cellular assays making this an ideal probe to study HDAC10 biology.

(last updated: 30 May 2024 )