Tubacin (tubulin acetylation inducer) is a small molecule that selectively inhibits histone deacetylase 6 (HDAC6) and induces acetylation of α-tubulin with IC50 of 0.004µM [1,2]. Tubacin also inhibited HDAC1 with IC50 of 1.4µM [2].
Tubacin preferentially induced α-tubulin hyperacetylation at 2.5 µM in BMSCs. Tubacin induces α-tubulin acetylation at 5 µM and protects prostate cancer (LNCaP) cells from hydrogen peroxide-induced death at 8 µM via peroxiredoxin acetylation [2]. Tubacin (0.25 µM and 0.5 µM) with a low concentrationcould promote BMSC adhesion, proliferation and migration, and tubacin can upregulate the protein levels of VCAM-1, ICAM-1, p-ERK, and acetylated α-tubulin [3]. Incubation with tubacin for 24 h increased the amount of Tumor-derived extracellular vesicles (EVs) in the conditioned media of both FEMX-I and Caco-2 cells by 6.6- and 2.1-fold, respectively [4]. Tubacin significantly altered the cellular lipid composition, which could promote release of CD133+ EVs in FEMX-1 and Caco-2 cells [4].
Tubacin (5 mg/kg, i.p.) significantly increased both mRNA and protein levels for eNOS in the aorta of mice, in the presence of NO donor sodium nitroprusside, tubacin's effects on Ach-mediated vasorelaxation were largely abolished [5]. Pretreatment with tubacin (5 mg/kg, i.p.) significantly reduced cerebral infarct size and the severity of cortical edema at 24 h after arterial occlusion [5]. Tubacin (5 mg/kg) administration significantly reduced the kidney growth in a very aggressive murine model of polycystic kidney disease (PKD)that features the development of giant polycystic kidneys at 3 weeks of age [6].
References:
[1]. Aldana-Masangkay G I, Rodriguez-Gonzalez A, Lin T, et al. Tubacin suppresses proliferation and induces apoptosis of acute lymphoblastic leukemia cells[J]. Leukemia & lymphoma, 2011, 52(8): 1544-1555.
[2]. Butler K V, Kalin J, Brochier C, et al. Rational design and simple chemistry yield a superior, neuroprotective HDAC6 inhibitor, tubastatin A[J]. Journal of the American Chemical Society, 2010, 132(31): 10842-10846.
[3]. Liang J Q, Lu F, Gan B, et al. Low-dose tubacin promotes BMSCs proliferation and morphological changes through the ERK pathway[J]. American Journal of Translational Research, 2019, 11(3): 1446.
[4]. Chao O S, Chang T C, Di Bella M A, et al. The HDAC6 inhibitor tubacin induces release of CD133+ extracellular vesicles from cancer cells[J]. Journal of Cellular Biochemistry, 2017, 118(12): 4414-4424.
[5]. Chen J, Zhang J, Shaik N F, et al. The histone deacetylase inhibitor tubacin mitigates endothelial dysfunction by up-regulating the expression of endothelial nitric oxide synthase[J]. Journal of Biological Chemistry, 2019, 294(51): 19565-19576.
[6]. Cebotaru L, Liu Q, Yanda M K, et al. Inhibition of histone deacetylase 6 activity reduces cyst growth in polycystic kidney disease[J]. Kidney international, 2016, 90(1): 90-99.