Fludarabine

別名:FaraA, Fludarabinum, NSC 118218

Fludarabine is a STAT1 activation inhibitor which causes a specific depletion of STAT1 protein (and mRNA) but not of other STATs. Also a DNA synthesis inhibitor in vascular smooth muscle cells. Fludarabine induces apoptosis.

Fludarabine化学構造

CAS No. 21679-14-1

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 29500 国内在庫あり
JPY 22000 国内在庫あり
JPY 55500 国内在庫あり
JPY 103500 国内在庫あり
JPY 220500 国内在庫なし(納期7~10日)

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製品安全説明書

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Fludarabine関連製品

シグナル伝達経路

STAT阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
EHEB Apoptosis Assay 40 μM 24 h induces apoptosis 23497075
HEC50B Apoptosis Assay 20/100 μM 24 h induces apoptosis slightly 23595697
AN3CA Apoptosis Assay 20/100 μM 24 h induces apoptosis in a dose-dependent manner 23595697
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生物活性

製品説明 Fludarabine is a STAT1 activation inhibitor which causes a specific depletion of STAT1 protein (and mRNA) but not of other STATs. Also a DNA synthesis inhibitor in vascular smooth muscle cells. Fludarabine induces apoptosis.
Targets
STAT1 [5]
(Vascular smooth muscle cells)
In Vitro
In vitro

Fludarabine efficiently inhibits the proliferation of RPMI 8226 cells with IC50 of 1.54 μg/mL. The IC50 of Fludarabine against MM.1S and MM.1R cells is 13.48 μg/mL and 33.79 μg/mL, respectively. In contrast, U266 cells are resistant to Fludarabine with IC50 of 222.2 μg/mL. Fludarabine treatment results in increased number of cells in the G1 phase of cell cycle, accompanied with a concomitant reduction of cells at the S phase of cell cycle in a time-dependent manner. Fludarabine induces a cell cycle block and triggers apoptosis in MM cells. Fludarabine triggers time-dependent cleavage of caspase-8, -9, and -3, -7, followed by PARP cleavage. Fludarabine increases expression of Bax in a time-dependent fashion, while the expression of Bak doesn't change. After exposure to Fludarabine for 12 hours, RPMI 8226 cells shows a loss of membrane potential with 61.05% of the cells expressing low fluorescence of rhodamine 123 compared with 8.62% of cells in untreated control. [1] To enhance solubility, Fludarabine is formulated as the monophosphate (F-ara-AMP, fudarabine), which is instantaneously and quantitatively dephosphorylated to the parent nucleoside upon intravenous infusion. Inside the cells rephosphorylation occurs which leads to fuoroadenine arabinoside triphosphate (F-ara-ATP), the major cytotoxic metabolite of F-ara-A. [2] Fludarabine can also induce pro-inflammatory stimulation of monocytic cells, as evaluated by increased expression of ICAM-1 and IL-8 release. [3] Fludarabine does not affect the growth of ovarian cancer cell lines, whereas it induces marked and dose-dependent inhibition of proliferation in melanoma cell lines. [4] Fludarabine is an inhibitor of STAT1 that specifically reduces STAT1 without affecting other STAT family members[5]. In addition to cytoplasmic accumulation, repeated low-dose cisplatin (RLDC) induces HMGB1 expression, which is marked suppressed by STAT1 knockdown. Consistently, fludarabine suppresses HMGB1 expression during RLDC treatment dose-dependently in RLDC-treat renal tubular cells[5].

細胞実験 細胞株 Dexamethasone-sensitive (MM.1S) and -resistant (MM.1R) human MM cell lines, RPMI8226 and U266 cell lines
濃度 2 μg/mL
反応時間 24 hours
実験の流れ

After treated with Fludarabine or control, dexamethasone-sensitive (MM.1S) and -resistant (MM.1R) human MM cell lines, RPMI8226 and U266 cell lines (5 × 105 cells) are washed twice in phosphate-buffered saline (PBS) and fixed with 70% ice-cold ethanol, then centrifuged and suspended in PBS containing 100 μg/mL RNase A. After incubated for 30 minutes at 37 ºC, samples are resuspended in 25 μg/mL propidium iodide. Flow cytometry is performed on a FACSCalibur automated system. Apoptosis is determined by Annexin V-FITC apoptosis detection kit, according to the manufacturer's instructions. For TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) assay, cells are analyzed by flow cytometry using the in situ cell death detection kit.

実験結果図 Methods Biomarkers 結果図 PMID
Western blot procaspase-9 / procaspase-3 p-p53 / p53 STAT1 27223263
Immunofluorescence α-SMA / Vimentin 28322315
Growth inhibition assay Cell viability 24956101
In Vivo
In Vivo

Tumors treated with PBS grow rapidly to approx-imately 10-fold their initial volume in 25 day, whereas, the tumors in the Fludarabine at 40 mg/kg increase less than 5-fold. A significant antitumor effect of 40 mg/kg Fludarabine on RPMI8226 tumor growth is demonstrated. RPMI8226 tumors treated with 40 mg/kg Fludarabine at day 10 increase apoptotic nuclei. Fludarabine is effective in suppressing RPMI8226 myeloma xenografts in SCID mice. [1]

動物実験 動物モデル Severe combined immunodeficient (SCID) mice bearing RPMI 8226 cells
投与量 40 mg/kg
投与経路 Administered via i.p.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05390814 Recruiting
Primary Central Nervous System Lymphoma
Assistance Publique - Hôpitaux de Paris
December 18 2023 Phase 1
NCT05201183 Withdrawn
Acute Myeloid Leukemia|Chronic Myeloid Leukemia|Acute Lymphocytic Leukemia|Myelodysplastic Syndromes
Naoyuki G. Saito M.D. Ph.D.|Indiana University
October 2023 Phase 1|Phase 2
NCT05917405 Recruiting
Acute Myeloid Leukemia in Remission
Nantes University Hospital
September 14 2023 Phase 2

化学情報

分子量 285.23 化学式

C10H12FN5O4

CAS No. 21679-14-1 SDF Download Fludarabine SDFをダウンロードする
Smiles C1=NC2=C(N=C(N=C2N1C3C(C(C(O3)CO)O)O)F)N
保管

In vitro
Batch:

DMSO : 57 mg/mL ( (199.83 mM); 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機
Clear solution
5%DMSO 40% 5% 50%ddH2O
4.0mg/ml (14.02mM) Taking the 1 mL working solution as an example, add 50 μL of 80 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. 

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

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よくある質問(FAQ)

質問1:
how to re-suspend and deliver the inhibitor for in vivo experiments?

回答
For S1491, Fludarabine, we tested a vehicle: 30% Propylene glycol, 5% Tween 80, 65% D5W that you can resuspend the compound in at up to 30mg/ml. It's a suspension and can only be given via oral gavage.

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