Tubastatin-A

Tubastatin-A : Inhibitor of Class IIB HDACs HDAC6, HDAC10

Structure

SERP Rating

In Cells

(2 ratings)

In Model Organisms

(2 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 Tubastatin-A is in the process of SERP review.

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Information

HDAC6
HDAC10

Inhibitor, Class IIB

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Probe Availability:

In Vitro Validations

Uniprot ID: Q9UBN7

Target Class: Epigenetic

Target SubClass: HDAC

Potency: IC 50

Potency Value: 15 nM

Potency Assay: Enzyme inhibition assays were performed by the Reaction Biology Corporation, Malvern, PA, using the Reaction Biology HDAC Spectrum platform and by TR-FRET following the displacement of radio-labelled compound.

PDB ID for probe-target interaction (3D structure): 6THV

Structure-activity relationship: yes, see 10.1021/acs.jmedchem.8b01936 for reference.

Target aliases:

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

DOI Reference: 10.1021/acs.jmedchem.8b01936

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : IC50 HDAC8 854 nM

Potency assay (off target): Enzyme inhibition assays using the Reaction Biology HDAC Spectrum platform.

Probe Selectivity in Vitro:

Enzyme inhibition assays using the Reaction Biology HDAC Spectrum platform.

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SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This compound has been claimed to be HDAC6 selective except by DOI: 10.1021/acs.jmedchem.8b01936 where this compound was shown to be more active in HDAC10 by FRET and BRET (cellular) assays

(last updated: 2 Jun 2020 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

The biology of HDAC6 and HDAC10 are likely to be very different so, this probe should be used in combination with genetic knockdown and/or other more selective compounds for either HDAC6 or HDAC10 (see for example Geraldy et al J. Med. Chem. 2019, 62, 9, 4426–4443) in order to attribute affects of Tubistatin A to one of these enzymes.

(last updated: 28 Jun 2020 )

Portal Comments

Tubastatin A has been used in >100 publications to probe HDAC6 biology under the assumption of high HDAC6 selectivity but according to Lechner S et al 2022 paper (DOI:10.1038/s41589-022-01015-5), Tubastatin A has a much higher potency for HDAC10 than HDAC6 (pKdapp, HDAC10 = 7.5 vs pKdapp, HDAC6 = 5.0). Additionally, metallo-β-lactamase domain-containing protein 2 (MBLAC2) as additional off-target for Tubastatin A with an affinity of below 1 µM.

(last updated: 25 May 2022)