Tubacin

Selective, Reversible Inhibitor of HDAC6

Structure

Information

Protein target names: HDAC6

Mechanism of action: Selective, Reversible Inhibitor

In Vitro Validations

Uniprot ID: Q9UBN7
Target Class: Epigenetic
Target SubClass: HDAC
Potency: Ki
Potency Value: 0.016 uM
Potency Assay: Biochemical enzyme assay with synthetic substrates (see Nature Chemical Biology paper)
PDB ID for probe-target interaction (3D structure): --
Target aliases:
Histone deacetylase 6, KIAA0901, HDAC6, HDAC6_HUMA ...

In Cell Validations

In Vivo Data

No in Vivo Validations

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SERP ratings and comments


SERP Ratings

In Cell Rating
In Model Organisms

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.

(last updated: 28 Apr 2017 )

SERP Ratings

In Cell Rating
In Model Organisms

Comments:

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.

(last updated: 11 May 2017 )

SERP Ratings

In Cell Rating

(last updated: 22 Jun 2017 )

Portal Comments

Tubacin and several other HDAC inhibitors have been independently profiled using a proteomics approach (Lechner et al). They identified metallo-β-lactamase domain-containing protein 2 (MBLAC2) as additional off-target for Tubacin with an affinity of about 1.7 µM.

Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target.

Lechner S, Malgapo MIP, Grätz C, Steimbach RR, Baron A, Rüther P, Nadal S, Stumpf C, Loos C, Ku X, Prokofeva P, Lautenbacher L, Heimburg T, Würf V, Meng C, Wilhelm M, Sippl W, Kleigrewe K, Pauling JK, Kramer K, Miller AK, Pfaffl MW, Linder ME, Kuster B, Médard G. Nat Chem Biol. 2022 Apr 28. doi: 10.1038/s41589-022-01015-5. 

(last updated: 8 Jun 2022)