Tubacin 

Tubacin is a potent and selective inhibitor of HDAC6, with an IC₅₀ value of 4 nM and approximately 350-fold selectivity over HDAC1. Tubacin also inhibits metallo-β-lactamase domain-containing protein 2 (MBLAC2).

Tubacin preferentially induces α-tubulin hyperacetylation at a concentration of 2.5 μM, and induces α-tubulin acetylation at 5 μM and protects prostate cancer (LNCaP) cells from hydrogen peroxide-induced death at 8 μM via peroxiredoxin acetylation^[1]. Tubacin (2.5 and 5 μM) specifically induces acetylation of α-tubulin in MM cells. Tubacin significantly inhibits both drug-sensitive and drug-resistant MM cell growth, with IC₅₀ 5-20 μM at 72 h. Tubacin also induces apoptosis by activation of caspases. Moreover, Tubacin inhibits binding of HDAC6 with dynein, and it induces significant accumulation of polyubiquitinated proteins, when combined with bortezomib. Tubacin and bortezomib induce synergistic antitumor activity in MM cell lines, and inhibits paracrine MM Cell Growth. Tubacin (5 μM) synergistically enhances bortezomib-induced cytotoxicity in patient MM cells without cytotoxicity to PBMCs^[2]. Tubacin can concentration-dependently inhibits JEV-induced cytopathic effect and apoptosis, as well as reduces virus yield in human cerebellar medulloblastoma cells. The IC₅₀ of virus yield is 0.26 μM for Tubacin. Tubacin also meaningfully blocks the production of intracellular infectious virus particles, with an IC₅₀ of 1.52 μM. Tubacin induces the hyperacetylation of a HDAC6 substrate Hsp90 and reduces the interaction of Hsp90 with JEV NS5 protein^[3].

MCE has not independently confirmed the accuracy of these methods. They are for reference only.

721.86

Solid

C₄₁H₄₃N₃O₇S

537049-40-4

OCC(C=C1)=CC=C1[C@@H]2C[C@H](CSC3=NC(C4=CC=CC=C4)=C(C5=CC=CC=C5)O3)O[C@H](C6=CC=C(NC(CCCCCCC(NO)=O)=O)C=C6)O2

Room temperature in continental US; may vary elsewhere.

• [1]. Butler KV, et al. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A. J Am Chem Soc. 2010 Aug 11;132(31):10842-6.  [Content Brief]

  [2]. Hideshima T, et al. Small-molecule inhibition of proteasome and aggresome function induces synergistic antitumor activity in multiple myeloma. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8567-72. Epub 2005 Jun 3.  [Content Brief]

  [3]. Lu CY, et al. Tubacin, an HDAC6 Selective Inhibitor, Reduces the Replication of the Japanese Encephalitis Virus via the Decrease of Viral RNA Synthesis. Int J Mol Sci. 2017 May 1;18(5).  [Content Brief]

  [4]. Severin Lechner, et al. Target deconvolution of HDAC pharmacopoeia reveals MBLAC2 as common off-target. Nat Chem Biol. 2022 Apr 28.  [Content Brief]