Cell lines

Human A549 lung carcinoma cells, Mouse NIH 3T3 wild-type (Neo), HDAC6, HDAC6 double-mutant, and HDAC6-overexpressing cells, Acute lymphoblastic leukemia (ALL) cells

Preparation method

Limited soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

2 μM, 4.5 h

Applications

In cultured cells, tubacin (10 μM) induced up to a 3-fold increase in the relative α-tubulin-acetylation level, with a half-maximum effective concentration (EC50) of 2.5 μM. Tubacin (2 μM) inhibited the migration of both wild-type and HDAC6-overexpressing cells. Tubacin treatment increased the colocalization of HDAC6 along acetylated microtubules in interphase cells. Treatment with tubacin led to the induction of apoptotic pathways in both pre-B and T cell ALL cells.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Tubacin is a potent, selective, reversible, and cell-permeable inhibitor of HDAC6 with an IC50 value of 4 nM.[1]
Histone deacetylases (HDACs) can be divided into 4 classes, among whom Class I, II, and IV is nuclear zinc-dependent enzymes and Class III is nicotinamide adenine dinucleotide (NAD+) dependent. HDACs catalyze deacetylation of N-acetyl-lysine residues and play an important role in a number of biological reactions including gene expression and cell cycle. By inhibiting α-tubulindeacetylation in mammalian cells, tubacin can suppress the expression of certain genes and therefore result in an antitumor effect without the level of histone acetylation. As selective inhibitors of HDAC6 are used in the treatment of protein degradation disorders, tubacin may have therapeutic applications as antimetastatic and antiangiogenic agent.[1,2]
Tubacin exhibited potent inhibition on HDAC6, with an IC50 value of 4 nM and approximately 350-fold selectivity over HDAC1. In cultured A549 cells, 10 μM tubacin induced up to a 3-fold increase in the relative α-tubulin- acetylation level, with an EC 50 of 2.5 μM. Acute lymphoblastic leukemia (ALL) and normal cells were treated with different concentrations of tubacin ranging from 0.5 to 2.5 mM or controls. The results indicated that tubacin inhibited the growth of ALL cells dose-dependently, with IC50 ranging from 1.2 to 2 mM. Moreover, ALL cells have a greater sensitivity to tubacin compared to other normal cells.[1,2,3]
Tuacin also showed suppressing activity in the growth of ALL cells in vivo. By treating pre-B ALL cells injected mice, the mice in experimental group survival were prolonged comparing with the control. Besides, tubacin treated HEK cells transfected with tau significantly attenuate tau phosphorylation at T231, which also revealed it may play an important role in the pathology of Alzheimer's Disease(AD). [3,4]
Reference:
1.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.
2.Haggarty S J, Koeller K M, Wong J C, et al. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation[J]. Proceedings of the National Academy of Sciences, 2003, 100(8): 4389-4394.
3.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.
4.Xu K, Dai X L, Huang H C, et al. Targeting HDACs: a promising therapy for Alzheimer's disease[J]. Oxidative medicine and cellular longevity, 2011, 2011.