WT161

製品コードS8495 バッチS849501

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₇H₃₀N₄O₃

分子量

458.55

CAS No.

1206731-57-8

Solubility (25°C)*

体外

DMSO

86 mg/mL (187.54 mM)

Ethanol

1 mg/mL (2.18 mM)

Water

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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	4.3mg/ml (9.38mM)	Taking the 1 mL working solution as an example, add 50 μL of 86 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	0.61mg/ml (1.33mM)	Taking the 1 mL working solution as an example, add 50 μL of 12.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

* <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	WT161は、強力で選択的かつ生物学的に利用可能なHDAC6阻害剤であり、HDAC6、HDAC1、およびHDAC2に対してそれぞれ0.4 nM、8.35 nM、および15.4 nMのIC50値を示し、他のHDACと比較して100倍以上の選択性を示します。WT161はアポトーシスを誘発します。
in vitro	WT161 selectively inhibits HDAC6 and dramatically increases levels of acetylated α-tubulin (Ac-α-tubulin) with little effect on global lysine acetylation. It induces accumulation of acetylated tubulin and cytotoxicity in multiple myeloma (MM) cells. This compound as a single agent does not induce ER stress, the UPR, or ER stress-mediated apoptosis. Consistent with this compound mediated hyperacetylation and inhibition of hsp90 chaperone function, treatment with this chemical increases the intracellular levels of polyubiuitylated proteins in the cultured MCL JeKo-1 and Z138 cells. It also dose-dependently depletes the levels of cyclin D1 in the cultured human Mantle Cell Lymphoma (MCL) cells. Treatment with this agent induces ER stress response in the MCL cells, demonstrated by increase in the protein levels of Glucose regulated protein (GRP) 78, phosphorylated eIF2 (eukaryotic initation factor 2) α, and induction of the pro-apoptotic transcription factor CHOP (CAAT/Enhancer Binding Protein Homologous Protein). This compound triggers apoptotic cell death in MCF7, T47D, BT474, and MDA-MB231 cells, associated with decreased expression of EGFR, HER2, and ERα and downstream signaling.
in vivo	WT161 has reasonable half-life in mice (1.4 h) and drug exposure [maximum concentration (Cmax) = 18 mg/L]. It is well tolerated as a single agent. This compound significantly inhibits in vivo MCF7 cell growth, associated with downregulation of ERα, in a murine xenograft model.

プロトコル(参考用のみ)

細胞アッセイ	細胞株	MM.1S cells
	濃度	3 µM
	反応時間	16 h
	実験の流れ	For annexin V-PI staining, MM.1S cells cultured for 16 h with BTZ (3 nM) and/or tubacin/WT161 (3 µM) are washed with PBS and processed.
動物実験	動物モデル	Female NCr nu/nu mice subcutaneously (sc) implanted with 17β-estradiol-sustained release pellets and inoculated s.c. with 5 × 106 MCF-7 cells suspended in 30% Matrigel
	投薬量	80 mg/kg
	投与方法	i.p.

参考

https://pubmed.ncbi.nlm.nih.gov/27799547/
http://www.bloodjournal.org/content/116/21/2856?sso-checked=true
https://pubmed.ncbi.nlm.nih.gov/29113288/

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：

In-Cell Testing of Zinc-Dependent Histone Deacetylase Inhibitors in the Presence of Class-Selective Fluorogenic Substrates: Potential and Limitations of the Method [ Biomedicines, 2024, 12(6)1203]	PubMed: 38927410
Epigenetic and molecular coordination between HDAC2 and SMAD3-SKI regulates essential brain tumour stem cell characteristics [ Nat Commun, 2023, 14(1):5051]	PubMed: 37598220
Incorporation of SKI-G-801, a Novel AXL Inhibitor, With Anti-PD-1 Plus Chemotherapy Improves Anti-Tumor Activity and Survival by Enhancing T Cell Immunity [ Front Pharmacol, 2022, 13:780179]	PubMed: 35330829
NADPH levels affect cellular epigenetic state by inhibiting HDAC3-Ncor complex [ Nat Metab, 2021, 3(1):75-89]	PubMed: 33462516

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。