Tubastatin A

製品コードS8049 バッチS804915

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C20H21N3O2
分子量 335.4 CAS No. 1252003-15-8
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 5 mg/mL (14.9 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Tubastatin A is a potent and selective HDAC6 inhibitor with IC50 of 15 nM in a cell-free assay. It is selective against all the other isozymes (1000-fold) except HDAC8 (57-fold). Tubastatin A promotes autophagy and increases apoptosis.
in vitro Tubastatin A is selective at all isozymes except HDAC8 and maintains over 1000-fold selectivity against all isoforms excluding HDAC8, where it has approximately 57-fold selectivity. This compound preferentially induces α-tubulin hyperacetylation at 2.5 μM. Slight induction of histone hyperacetylation is seen for this chemical at 10 μM. It displays dose-dependent protection against homocysteic acid-induced neuronal cell death starting at 5 μM with near complete protection at 10 μM. [1] This compound (10 μM) induces an increase in acetylated-α-tubulin levels and the restoration of primary cilia expression in the cholangiocarcinoma cell lines (18-fold); and the restoration of primary cilia correlated with downregulated Hedgehog (Hh) and MAPK signaling pathways, as well as decreased cell proliferation rates (in average by 50%) and invasion (by 40%). [2] It shows significant inhibition of TNF-α and IL-6 in LPS stimulated human THP-1 macrophages with an IC50 of 272 nM and 712 nM. This inhibitor inhibits nitric oxide (NO) secretion in murine Raw 264.7 macrophages dose depenndently with an IC50 of 4.2 μM. [3]
in vivo Tubastatin A reduces the growth of cholangiocarcinoma in vivo. This compound (10 mg/kg) induces a 6-fold lower mean tumor weights in syngeneic rat orthotopic model of cholangiocarcinoma, and reduction of the ratios of tumor weight to liver weight and body weight (5- and 5.6-fold, respectively), as well as a greater frequency of ciliated cholangiocytes compared with controls (29% vs 1.4%). It significantly decreases the amount of PCNA-positive cells in the treated tumors compared with vehicle controls (34% vs 65%). [2] This chemical shows significant inhibition of paw volume at 30 mg/kg i.p. in a Freund's complete adjuvant (FCA) induced animal model of inflammation. It (30 mg/kg i.p.) significant attenuates clinical scores (~ 70%), and IL-6 expression in paw tissues of collagen induced arthritis DBA1 mouse. [3]

プロトコル(参考用のみ)

キナーゼアッセイ HDAC enzymatic assays
Tubastatin A is dissolved and diluted in assay buffer (50 mM HEPES, pH 7.4, 100 mM KCl, 0.001% Tween-20, 0.05% BSA, and 20 μM tris(2-carboxyethyl)phosphine) to 6-fold of the final concentration. HDAC enzymes are diluted to 1.5-fold of the final concentration in assay buffer and pre-incubated with this compound for 10 minutes before the addition of the substrate. The amount of FTS (HDAC1, HDAC2, HDAC3, and HDAC6) or MAZ-1675 (HDAC4, HDAC5, HDAC7, HDAC8, and HDAC9) used for each enzyme is equal to the Michaelis constant (Km), as determined by a titration curve. FTS or MAZ-1675 is diluted in assay buffer to 6-fold the final concentration with 0.3 μM sequencing grade trypsin. The substrate/trypsin mix is added to the enzyme/compound mix and the plate is shaken for 60 seconds and then placed into a SpectraMax M5 microtiter plate reader. The enzymatic reaction is monitored for release of 7-amino-4-methoxy-coumarin over 30 minutes, after deacetylation of the lysine side chain in the peptide substrate, and the linear rate of the reaction is calculated.
細胞アッセイ 細胞株 Human cholangiocarcinoma cell lines HuCCT-1
濃度 ~10 μM
反応時間 21 days
実験の流れ Anchorage-independent growth is assessed by growing cells in soft agar. About 25,000 cells suspended in 0.4% agar in culture media are layered over a 1% agar layer in a 6-well plate. Media are added twice a week and pictures are taken after 21 days of incubation. The number and size of colonies are analyzed using the Gel-Pro software.
動物実験 動物モデル Rat cholangiocarcinoma xenografts BDEneu
投薬量 10 mg/kg
投与方法 i.p. daily

参考

  • https://pubmed.ncbi.nlm.nih.gov/20614936/
  • https://pubmed.ncbi.nlm.nih.gov/23370327/
  • https://pubmed.ncbi.nlm.nih.gov/23541634/
  • https://pubmed.ncbi.nlm.nih.gov/22262760/

カスタマーフィードバック

Data from [Data independently produced by Nat Commun, 2014, 5, 3479]

Data from [Data independently produced by Int J Cancer, 2014, 134(11):2560-71]

Data from [J Biol Chem, 2013, 288(20), 14400-7]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Reprogramming aerobic metabolism mitigates Streptococcus pyogenes tissue damage in a mouse necrotizing skin infection model [ Nat Commun, 2025, 16(1):2559] PubMed: 40089471
HSD17B4 deficiency causes dysregulation of primary cilia and is alleviated by acetyl-CoA [ Nat Commun, 2025, 16(1):2663] PubMed: 40102401
CITK modulates BRCA1 recruitment at DNA double strand breaks sites through HDAC6 [ Cell Death Dis, 2025, 16(1):320] PubMed: 40254670
Primary cilia prevent activation of the cGAS-STING pathway during mouse decidualization [ Commun Biol, 2025, 8(1):607] PubMed: 40229503
The Role of Primary Cilia in Modulating the Luteinization Process of Ovarian Granulosa Cells in Mice [ Int J Mol Sci, 2025, 26(5)2138] PubMed: 40076758
Donepezil-induced degradation of hERG potassium channel via lysosomal pathway is exacerbated by hypoxia [ Eur J Pharmacol, 2025, 996:177549] PubMed: 40157707
Inhibition of HDAC6 elicits anticancer effects on head and neck cancer cells through Sp1/SOD3/MKP1 signaling axis to downregulate ERK phosphorylation [ Cell Signal, 2025, 127:111587] PubMed: 39755348
Rapid and sustained antidepressant effects of tubastatin A in a mouse model of depression [ Sci Rep, 2025, 15(1):5182] PubMed: 39939731
Genotype-Phenotype Distinctions in Spastic Paraplegia 4 Reveal HDAC6 as a Therapeutic Target [ bioRxiv, 2025, 2025.07.15.664947] PubMed: 40791524
HDAC6-dependent deacetylation of NGF dictates its ubiquitination and maintains primordial follicle dormancy [ Theranostics, 2024, 14(6):2345-2366] PubMed: 38646645

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。