Tubacin

Reagent Authentication Certificate:

Chemical Probes Portal Tubacin.pdf

Protein target name:

HDAC6

Recommended Concentration for use in cells:

Up to 200 nM

Probe Availability

Tocris (1350555-93-9)

MedChem Express (537049-40-4)

Cayman (537049-40-4)

Probe Information

Target and Probe Information

Target Details

Target class:

Epigenetics

Subclass:

HDAC

HUGO symbol:

HDAC6

Entrez gene ID:

10013

Target alias:

Histone deacetylase 6, CPBHM, HD6, JM21, PPP1R90

Probe Details

Chemical Probes Portal ID:

CPP1487

PubChem CID:

6675804

ChEMBL ID:

CHEMBL356769

SMILES string:

C1[C@@H](O[C@@H](O[C@@H]1C2=CC=C(C=C2)CO)C3=CC=C(C=C3)NC(=O)CCCCCCC(=O)NO)CSC4=NC(=C(O4)C5=CC=CC=C5)C6=CC=CC=C6

InChi Key:

BHUZLJOUHMBZQY-YXQOSMAKSA-N

Control compound:

niltubacin

Validation in Cells and Model Organisms

In vitro validation

On target activity

Potency:

0.016 uM

Potency assay:

Biochemical enzyme assay with synthetic substrates (see Nature Chemical Biology paper)

Off target activity

Potency (off target):

Off target protein and potency:

HDAC1: 0.028 uM, HDAC2: 0.042 uM, HDAC3: 0.275 uMHDAC4: 17 uM, HDAC5: 1.5 uM, HDAC7: 8.5 uMHDAC8: 0.17 uM

In cell validation

On target activity in cells

Potency in cells:

EC50

2.5 uM

Potency assay (cells):

Tubulin acetylation assays

Target engagement assay (cells):

Indirect, substrate acetylation assays

Off target activity in cells

Potency assay, off target (cells):

Tubacin had no affect on cellular morphology (microtubules) in A549 cells. Tubacin did not lead to changes in gene expression (1.3-fold threshold). Tubacin did not impact the cell cycle or the mitotic spindle. In cells expressing HDAC6, tubacin increased levels of alpha-tubulin acetylation. Overexpression of HDAC6 but not an inactive mutant of HDAC6 decreased the sensitivity of cells to tubacin.

Primary Reference

Reference (doi):

10.1073/pnas.0430973100 10.1016/S1074-5521(03)00095-4 1038/nchembio.313

Reference (PMID):

12677000 12770821 20139990

SAB Rating

Rating for use in Cells

3 review(s)

Rating for use in Model Organisms

3 review(s)

SAB Members

SAB Comments

Tubacin (tubulin acetylation inducer) is a small molecule that inhibits histone deacetylase 6 (HDAC6) and induces acetylation of α-tubulin. The use of Tubacin in models of disease has helped to validate, in part, HDAC6 as a drug target, but its non-drug-like structure, high lipophilicity conspire to make it more useful as a research tool than a drug. Tubacin was found to potently inhibit HDAC6, with an IC50 value of 4 nM and approximately 350-fold selectivity over HDAC1. Tubacin induced alpha-tubulin hyperacetylation at ~2.5 to 10 μM concentrations.

Even though tubacin was the first HDAC6 inhibitor identified that targets tubulin acetylation 14 years ago, it remains of great interest, particularly as an antitumor and neuroprotective agent. It is a potent, selective HDAC6 inhibitor. Tubacin was found to inhibit the deacetylation of alpha-tubulin in mammalian cells without affecting histone acetylation, gene expression or cell-cycle progression. An interesting feature of tubacin is the lack of toxicity for normal haematological cells. As a result of its non drug-like structure (MW= 721, PSA 139, ClogP 4.85, 4 HBD, rotatable bonds > 10), tubacin is administered intraperitoneally and is more a useful research tool than a drug.

Tubacin

Probe Availability

Probe Information

Target Details

Histone deacetylase 6, CPBHM, HD6, JM21, PPP1R90

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

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Tubacin

Probe Availability

Probe Information

Target Details

Histone deacetylase 6, CPBHM, HD6, JM21, PPP1R90

Probe Details

In vitro validation

In cell validation

Primary Reference

Supporting Organizations

Interested in supporting the portal?