SGC-UBD253

SGC-UBD253 : Inhibitor of HDAC6

Structure

SERP Rating

In Cells

(1 ratings)

In Model Organisms

(0 ratings)

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Probe SGC-UBD253 is in the process of SERP review.

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Information

HDAC6

Inhibitor

up to 10 uM

Additional Data

SGC Chemical Probe Collection

In Vitro Validations

Uniprot ID: Q9UBN7

Target Class: Epigenetic

Target SubClass: HDAC

Potency: Kd

Potency Value: 84 nM

Potency Assay: SPR with HDAC6 Ubiquitin Binding Domain

PDB ID for probe-target interaction (3D structure): 8G45

Target aliases:

Histone deacetylase 6, KIAA0901, HDAC6, HDAC6_HUMA ...

DOI Reference: 10.1021/acs.jmedchem.3c00314

Uniprot ID: Q9UBN7

Target Class: Epigenetic

Target SubClass: HDAC

Potency: Kd

Potency Value: 80 nM

Potency Assay: ITC

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

Target aliases:

Histone deacetylase 6, KIAA0901, HDAC6, HDAC6_HUMA ...

DOI Reference: 10.1021/acs.jmedchem.3c00314

Uniprot ID: Q9UBN7

Target Class: Epigenetic

Target SubClass: HDAC

Potency: IC50

Potency Value: 95 nM

Potency Assay: Fluorescence Polarisation Assay

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

Target aliases:

Histone deacetylase 6, KIAA0901, HDAC6, HDAC6_HUMA ...

DOI Reference: 10.1021/acs.jmedchem.3c00314

In Cell Validations

In Vivo Data

No in Vivo Validations

Off-Target Selectivity Assesments

Potency assay (off target): Using sequence alignment of Zf-UBD pocket, 10 UBD-containing proteins in addition to HDAC6 were purified and tested for direct binding by SPR. SGC-UBD253 was at least ~50-fold selective for HDAC6 over other UBD proteins tested, with the exception of USP16, for which it is 15-fold selective.

Potency assay, off target (cells): NanoBRET assay was designed to assess USP16-ISG15 interaction. Similar to the HDAC6 NanoBRET assay, an ISG15-binding deficient mutant of USP16 (R84A/Y117A) was used to define the baseline of the assay. An EC50 of 20 ± 2.7 µM was determined using this assay in HEK293T cells, indicating approximately 10-fold selectivity of 25 for HDAC6 over USP16 under these conditions.

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SERP ratings and comments

SERP+ Ratings

In Cell Rating

SERP+ Comments:

SGC-UBD253 can be a useful orthogonal tool for exploring HDAC6. It also has a negative control compound, which can be very helpful. However, further cellular characterization is still necessary. It should be noted that there is a good alternative chemical probe called SS-208.

(last updated: 23 Sept 2024 )