Niltubacin, as an inactive derivative of Tubacin, is a highly potent and selective, reversible cell-permeable inhibitor of HDAC6.
Niltubacin, as an inactive derivative of Tubacinis, is a highly potent and selective, reversible cell-permeable inhibitor of HDAC6. Histone deacetylase 6 (HDAC6) is structurally and functionally unique among the 11 human zinc-dependent histone deacetylases. HDAC6-selective inhibitor tubacin significantly enhances cell death induced by the topoisomerase II inhibitors etoposide and doxorubicin and the pan-HDAC inhibitor SAHA (vorinostat) in transformed cells (LNCaP, MCF-7), an effect not observed in normal cells. The inactive analogue of tubacin, nil-tubacin, does not sensitize transformed cells to these anticancer agents.
|方法||Cell adhesion assay Prior to SDF-1α (100 ng/ml) stimulation, Raji cells were treated with DMSO, NaB (1 μM), or tubacin (1 μM) for 3 hours. Then cells were plated into a 96-well plate which were precoated with Fibronectin (50 ng/ml) to allow cell adherence for 30 minutes. Subsequently cells were washed with PBS three times to remove the non-adherent cells, and adherent cells were measured by CellTiter-Glo luminescent cell viability assay kit.|
|动物模型||PLD animal model 3-week-old PCK rats|
|剂量||30 mg/kg body|
|动物 A (mg/kg) = 动物 B (mg/kg) ×||动物 B的Km系数|
例如，依据体表面积折算法，将白藜芦醇用于小鼠的剂量22.4 mg/kg 换算成大鼠的剂量，需要将22.4 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到白藜芦醇用于大鼠的等效剂量为11.2 mg/kg。
|溶解性（25°C）||DMSO ≥5 mg/mL|
固体粉末： -20°C 冷藏长期储存
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.4147 mL||7.0736 mL||14.1473 mL|
|5 mM||0.2829 mL||1.4147 mL||2.8295 mL|
|10 mM||0.1415 mL||0.7074 mL||1.4147 mL|
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Prominin-1 controls stem cell activation by orchestrating ciliary dynamics.
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Activated Transcription Factor 3 in Association with Histone Deacetylase 6 Negatively Regulates MicroRNA 199a2 Transcription by Chromatin Remodeling and Reduces Endothelin-1 Expression.
|数据来源||J Cell Biochem (2017). Figure 5. Niltubacin (Abmole Bioscience Inc.)|
|方法||Clonogenic survival assay|
|细胞系||FEMX-I cell line|
|实验结果||This effect was specific for tubacin, as TSA, niltubacin and ACY-1215 did not inhibit the formation of cell aggregates. Similar effects were observed in Caco-2 cell line (Supplementary Fig. S5).|
|数据来源||J Cell Biochem (2017). Figure 2. Niltubacin (Abmole Bioscience Inc.)|
|方法||Cell Aggregation Assay|
|细胞系||FEMX-I cell line|
|实验结果||The effect was specific, as the inactive analog of tubacin, niltubacin, at the same concentration did not increase CD133, CD9, or b-actin levels (Fig. 2c).|
|数据来源||Mol. Cell. Biol. (2016). Figure 9. Tubacin and Niltubacin for animal studies were obtained from AbMole Bioscience Inc. (Houston, TX)|
|处理时间||5 or 10 or 30 days|
|实验结果||These drug regimens showed a time dependent reduction of PlGF (Fig. 9C) and ET-1 (Fig. 9D) in plasma, compared to Niltubacin. The 30 day drug treatment effectively reduced plasma levels of PlGF by ~60% (p <0.001, Fig. 9C) and plasma levels of ET-1 by ~60% (p<0.001, Fig. 9D).|
|数据来源||Mol. Cell. Biol. (2016). Figure 7. Tubacin and Niltubacin for animal studies were obtained from AbMole Bioscience Inc. (Houston, TX)|
|实验结果||Taken together, these data showed PlGF induced chromatin condensation to repress DNM3os transcription, while Tubacin prevented the repressive effect following PlGF signaling.|
|数据来源||Mol. Cell. Biol. (2016). Figure 6. Tubacin and Niltubacin for animal studies were obtained from AbMole Bioscience Inc. (Houston, TX)|
|方法||qRT-PCR and reporter luciferase activity|
|实验结果||We concluded that HDAC6 required functional ATF3 binding sites in the DNM3os promoter and any antagonism of PlGF effects by Tubacin was not due to a general effect on transcription of the endogenous DNM3os gene or the wt DNM3os reporter construct.|
Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents.
Namdar et al. Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):20003-8. PMID: 21037108.
Histone deacetylase 6 interacts with the microtubule-associated protein tau.
Ding et al. J Neurochem. 2008 Sep;106(5):2119-30. PMID: 18636984.
|4-Phenylbutyric acid (4-PBA)
4-Phenylbutyric acid（4-PBA）是一种HDAC的抑制剂，在2 mM时可以抑制多种非小细胞肺癌细胞。
Tasquinimod is an oral antiangiogenic agent, it is also a S100A9 inhibitor.
BG45是一个选择性的HDAC3抑制剂 (IC50=289 nM)，但对HDAC1/2/6的抑制效力则显著降低 (IC50分别为2，2.2和 >20μM)。
Givinostat 是一种HDAC抑制剂，其对HDAC1和HDAC3的IC50值分别为198 nM和157 nM。