Tubacin
(Synonyms: HDAC6抑制剂) 目录号 : GC16386
Tubacin (tubulin acetylation inducer)是一种选择性抑制组蛋白去乙酰化酶6 (HDAC6)，诱导α-微管蛋白乙酰化的小分子，IC50为0.004µM。
Cas No.:537049-40-4
Sample solution is provided at 25 µL, 10mM.
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- Purity: >95.00%
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| Cell experiment [1]: | |
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Cell lines |
canine renal epithelial cells MDCK.2 cells |
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Preparation Method |
Confluent MDCK.2 cells were split 1:10 in 10-cm dishes. After 24 hours, the cells were again split, resuspended in 10 ml of medium, and pelleted. They were resuspended in 2 ml of medium, and 2 × 104 cells were mixed with growth factor-reduced Matrigel (1.5%) and collagen I (1.5%), MEM (1×), HEPES (20 µM), and NaHCO3 (0.24%). The Matrigel/collagen I/cell mixture was plated in 24-well plates (450 µl/well) and allowed to solidify for 30 minutes at 37°C before being overlaid with 500 µl of medium. Cells were treated with tubacin, tubastatin-A, or DMSO dissolved in medium on days 0, 2, 4, 6, 8, 10, 12, and 14 after old medium was removed. |
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Reaction Conditions |
10 µM for 0-14 d |
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Applications |
Treated the cells with tubacin on days 0, 2, 4, 6, 8, 10, 12, and 14, and this treatment did indeed prevent cyst formation. treated the cells only once with tubacin, on day 0, this single treatment alone slowed the cyst growth. |
| Animal experiment [2]: | |
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Animal models |
Colitis models |
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Preparation Method |
Freshly prepared 4% (wt/vol) dextran sodium sulfate (DSS) was added daily for 5 days to the pH-balanced tap water of WT B6 mice. Mice were treated daily for 7 days with tubacin or niltubacin (0.5 mg/kg of body weight/day, i.p.), and colitis was assessed by daily monitoring of body weight, stool consistency, and fecal blood. Stool consistency was scored as 0 (hard), 2 (soft), or 4 (diarrhea), and fecal blood (Hemoccult) was scored as 0 (absent), 2 (occult), or 4 (gross). |
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Dosage form |
Intraperitoneal injection, 0.5 mg/kg/day |
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Applications |
Tubacin-treated mice were protected against development of weight loss and diarrhea, and this effect was Treg dependent. |
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References: [1]: 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. | |
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.
| Cas No. | 537049-40-4 | SDF | |
| 别名 | HDAC6抑制剂 | ||
| 化学名 | N-[4-[(2R,4R,6S)-4-[(4,5-diphenyl-1,3-oxazol-2-yl)sulfanylmethyl]-6-[4-(hydroxymethyl)phenyl]-1,3-dioxan-2-yl]phenyl]-N'-hydroxyoctanediamide | ||
| Canonical SMILES | C1C(OC(OC1C2=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 | ||
| 分子式 | C41H43N3O7S | 分子量 | 721.86 |
| 溶解度 | ≥ 7.19mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.3853 mL | 6.9266 mL | 13.8531 mL |
| 5 mM | 0.2771 mL | 1.3853 mL | 2.7706 mL |
| 10 mM | 0.1385 mL | 0.6927 mL | 1.3853 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Low-dose tubacin promotes BMSCs proliferation and morphological changes through the ERK pathway
Am J Transl Res2019 Mar 15;11(3):1446-1459.PMID: 30972173DOI: 10.3109/10428194.2011.570821
Histone deacetylase 6 (HDAC6) plays critical roles in many cellular processes related to cancer, but its epigenetic regulation in bone marrow stromal stem cells (BMSCs) remains unexplored. This study investigated the beneficial effects of Tubulin Acetylation Inducer (tubacin), a novel specific HDAC6 inhibitor, on the proliferation and migration of BMSCs. A low concentration of tubacin promoted BMSC commitment and enhanced proliferation of BMSCs. Atomic force microscopy results showed that tubacin induced morphological changes and enhanced the mechanical properties of BMSCs. Furthermore, low tubacin concentrations significantly upregulated protein expression of acetylated α-tubulin, VCAM-1, and ICAM-1, which could be suppressed by an ERK inhibitor. Protein chip analysis showed that there were significant changes in the expression levels of 49 cytokines after tubacin treatment, which participate in inflammatory responses and cell activation, proliferation, and differentiation. Our findings suggest that the protective effects of tubacin on BMSCs involve HDAC6 inhibition by activating the ERK pathway.
Tubacin suppresses proliferation and induces apoptosis of acute lymphoblastic leukemia cells
Leuk Lymphoma2011 Aug;52(8):1544-55.PMID: 21699378DOI: 10.3109/10428194.2011.570821
Over the past decade, histone deacetylase inhibitors have increasingly been used to treat various malignancies. Tubacin (tubulin acetylation inducer) is a small molecule that inhibits histone deacetylase 6 (HDAC6) and induces acetylation of α-tubulin. We observed a higher antiproliferative effect of tubacin in acute lymphoblastic leukemia (ALL) cells than in normal hematopoietic cells. Treatment with tubacin led to the induction of apoptotic pathways in both pre-B and T cell ALL cells at a 50% inhibitory concentration (IC(50)) of low micromolar concentrations. Acetylation of α-tubulin increases within the first 30 min following treatment of ALL cells with tubacin. We also observed an accumulation of polyubiquitinated proteins and poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, the signaling pathways activated by tubacin appear to be distinct from those observed in multiple myeloma. In this article, we demonstrate that tubacin enhances the effects of chemotherapy to treat primary ALL cells in vitro and in vivo. These results suggest that targeting HDAC6 alone or in combination with chemotherapy could provide a novel approach to treat ALL.
Tubacin, an HDAC6 Selective Inhibitor, Reduces the Replication of the Japanese Encephalitis Virus via the Decrease of Viral RNA Synthesis
Int J Mol Sci2017 May 1;18(5):954.PMID: 28468311DOI: 10.3390/ijms18050954
Japanese encephalitis virus (JEV), a neurotropic flavivirus, annually causes over 30,000 Japanese Encephalitis (JE) cases in East and Southeast Asia. Histone deacetylases (HDACs) modulate lysine acetylation of histones and non-histone proteins, regulating many processes including inflammation and antiviral immune response. This study investigated antiviral activity of pan- and selective-HDAC inhibitors as host-targeting agents against JEV. Among HDAC inhibitors, selective HDAC6 inhibitors (tubastatin-A (TBSA) and tubacin) concentration-dependently inhibited JEV-induced cytopathic effect and apoptosis, as well as reduced virus yield in human cerebellar medulloblastoma cells. The 50% inhibitory concentration (IC50) values of virus yield was 0.26 μM for tubacin and 1.75 μM for TBSA, respectively. Tubacin (IC50 of 1.52 μM), but not TBSA, meaningfully blocked the production of intracellular infectious virus particles. In time-of-addition assays, the greatest potency of antiviral activity was observed in the mode of pre-treatment with tubacin (IC50 of 1.89 μM) compared to simultaneous (IC50 of 4.88 μM) and post-treatment (IC50 of 2.05 μM) modes. Interestingly, tubacin induced the hyperacetylation of a HDAC6 substrate Hsp90 and reduced the interaction of Hsp90 with JEV NS5 protein. Novobiocin, an Hsp90 inhibitor, diminished the NS5 protein amount and virus replication in JEV-infected cells. Meantime, tubacin suppressed the NS5 expression and antisense RNA genome synthesis in infected cells. Tubacin-induced Hsp90 hyperacetylation was suggested to influence the NS5 activity in JEV replication. Therefore, tubacin had a high potential of a host-targeting agent against JEV, exhibiting preventive and therapeutic activities against JEV infection.
Tubacin kills Epstein-Barr virus (EBV)-Burkitt lymphoma cells by inducing reactive oxygen species and EBV lymphoblastoid cells by inducing apoptosis
J Biol Chem2009 Jun 19;284(25):17102-17109.PMID: 19386607DOI: 10.1074/jbc.M809090200
Tubacin is a small molecule inhibitor of histone deacetylase 6 and blocks aggresome activity. We found that Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL) cells were generally killed by lower doses of tubacin than EBV-transformed lymphoblastoid cells (LCLs) or EBV-negative BL cells. Tubacin induced apoptosis of LCLs, which was inhibited by pretreatment with a pancaspase inhibitor but not by butylated hydroxyanisole, which inhibits reactive oxygen species. In contrast, tubacin killed EBV-positive BL cells in a caspase-3-independent pathway that involved reactive oxygen species and was blocked by butylated hydroxyanisole. Previously, we showed that bortezomib, a proteasome inhibitor, induces apoptosis of EBV LCLs and that LCLs are killed by lower doses of bortezomib than EBV-positive BL cells. Here we found that the combination of bortezomib and tubacin acted in synergy to kill EBV-positive BL cells and LCLs. Tubacin or the combination of bortezomib and tubacin did not induce EBV lytic replication. These findings suggest that the combination of a proteasome inhibitor and an HDAC6 inhibitor may represent a useful strategy for the treatment of certain EBV-associated B cell lymphomas.
The histone deacetylase inhibitor tubacin mitigates endothelial dysfunction by up-regulating the expression of endothelial nitric oxide synthase
J Biol Chem2019 Dec 20;294(51):19565-19576.PMID: 31719145DOI: 10.1074/jbc.RA119.011317
Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo We found that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found that these effects were not mediated by tubacin's inhibitory effect on HDAC6 activity, but rather were due to its ability to stabilize eNOS mRNA transcripts. Consistent with these findings, tubacin also inhibited proinflammatory cytokine-induced degradation of eNOS transcripts and impairment of endothelium-dependent relaxation in the mouse aorta. Furthermore, we found that tubacin-induced up-regulation in eNOS expression in vivo is associated with improved endothelial function in diabetic db/db mice and with a marked attenuation of ischemic brain injury in a murine stroke model. Our findings indicate that tubacin exhibits potent eNOS-inducing effects and suggest that this compound might be useful for the prevention or management of endothelial dysfunction-associated cardiovascular diseases.