Tubastatin A

製品コードS8049 バッチS804917

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 67 mg/mL warmed with 50ºC water bath (199.76 mM)
Water Insoluble
Ethanol Insoluble
* <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. Tubastatin A preferentially induces α-tubulin hyperacetylation at 2.5 μM. Slight induction of histone hyperacetylation is seen for Tubastatin A at 10 μM. Tubastatin A displays dose-dependent protection against homocysteic acid-induced neuronal cell death starting at 5 μM with near complete protection at 10 μM. [1] Tubastatin A (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] Tubastatin A 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. Tubastatin A 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. Tubastatin A (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%). Tubastatin A significantly decreases the amount of PCNA-positive cells in the treated tumors compared with vehicle controls (34% vs 65%). [2] Tubastat A shows significant inhibition of paw volume at 30 mg/kg i.p. in a Freund's complete adjuvant (FCA) induced animal model of inflammation. Tubastat A (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 Tubastatin A 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

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：

Integrated drug response prediction models pinpoint repurposed drugs with effectiveness against rhabdomyosarcoma [ PLoS One, 2024, 19(1):e0295629] PubMed: 38277404
HDAC Inhibition Induces CD26 Expression on Multiple Myeloma Cells via the c-Myc/Sp1-mediated Promoter Activation [ Cancer Res Commun, 2024, 4(2):349-364] PubMed: 38284882
α-Tubulin detyrosination links the suppression of MCAK activity with taxol cytotoxicity [ J Cell Biol, 2023, 222(2)e202205092] PubMed: 36459065
Selectivity of Hydroxamate- and Difluoromethyloxadiazole-Based Inhibitors of Histone Deacetylase 6 In Vitro and in Cells [ Int J Mol Sci, 2023, 24(5)4720] PubMed: 36902164
Shortening of primary cilia length is associated with urine concentration in the kidneys [ Kidney Res Clin Pract, 2023, 42(3):312-324] PubMed: 37313611
Reprogramming Short-Chain Fatty Acid Metabolism Mitigates Tissue Damage for Streptococcus pyogenes Necrotizing Skin Infection [ Res Sq, 2023, rs.3.rs-3689163] PubMed: 38196634
Corroborating evidence for aberrant expression of histone deacetylase 8 in endometriosis [ Reprod Med Biol, 2023, 22(1):e12527] PubMed: 37476367
Corroborating evidence for aberrant expression of histone deacetylase 8 in endometriosis [ Reprod Med Biol, 2023, 10.1002/rmb2.12527] PubMed: 37476367
Protective effect of HDACIs in improves survival and organ injury after CLP-induced sepsis [ Surg Open Sci, 2023, 12:35-42] PubMed: 36936452
Actin-microtubule cytoskeletal interplay mediated by MRTF-A/SRF signaling promotes dilated cardiomyopathy caused by LMNA mutations [ Nat Commun, 2022, 13(1):7886] PubMed: 36550158

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