Fludarabine

An intermediate active metabolite of fludarabine

此产品仅用于科学研究，我们不为任何个人用途提供产品和服务

库存: 现货

可选规格

包装

价格

促销价

数量
10mg

￥637.00

510.00

- +
50mg

￥1837.00

1470.00

- +
200mg

￥3787.00

3030.00

- +

已选 0 种 0 瓶

金额: ￥0.00

首页收藏

Background

Fludarabine is a purine analog that inhibits DNA synthesis [1].

DNA synthesis is a natural creation of deoxyribonucleic acid (DNA) molecules and plays an important role in cell growth.

Fludarabine is a prodrug and is phosphorylated to the nucleoside triphosphate (F-ara-ATP) in cells to elicit biological activity. It affected a series of enzymes that required in DNA synthesis such as DNA primase, DNA polymerases, DNA ligase I, ribonucleotide reductase and 3’-5’ exonuclease activity of DNA polymerases δ and ε [1]. In human myeloma cell RPMI8226, fludarabine significantly inhibited cells growth and reduced phosphorylation of Akt. Also, it reduced XIAP and survivin, the inhibitors of apoptosis proteins (IAP) family [2]. Fludarabine can act as a cytosolic 50-nucleotidase II (cN-II) inhibitor [3].

In immunodeficient mice bearing RPMI8226 myeloma xenografts, fludarabine (40 mg/kg) slowed down the growth of tumors by about 5-fold in 25 d comparing with the control tumors [2].

参考文献:
[1].? Gandhi V, Huang P, Plunkett W. Fludarabine inhibits DNA replication: a rationale for its use in the treatment of acute leukemias. Leuk Lymphoma, 1994, 14 Suppl 2: 3-9.
[2].? Meng H, Yang C, Ni W, et al. Antitumor activity of fludarabine against human multiple myeloma in vitro and in vivo. Eur J Haematol, 2007, 79(6): 486-493.
[3].? Cividini F, Pesi R, Chaloin L, et al. The purine analog fludarabine acts as a cytosolic 5'-nucleotidase II inhibitor. Biochem Pharmacol, 2015, 94(2): 63-68.

Protocol

Cell experiment [1]:
Cell lines	RPMI 8226 cells
Preparation method	The solubility of this compound in DMSO is > 9.3 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 °C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 °C for several months.
Reacting condition	1, 2 or 4 μg/mL; 6, 12 or 24 hrs
Applications	Fludarabine potently inhibited the proliferation of RPMI 8226 cells in dose- and time-dependent manners, with an IC50 value of 1.54 μg/mL. Fludarabine arrested RPMI 8226 cells in the G1 phase of cell cycle and triggered apoptosis. The immunoblotting results showed that Fludarabine time-dependently induced cleavage of caspase-8, -9, -3 and -7, followed by PARP cleavage. In addition, Fludarabine time-dependently up-regulated Bax expression, without affecting Bak expression.
Animal experiment [1]:
Animal models	SCID mice bearing RPMI 8226 cells
Dosage form	40 mg/kg; i.p.
Applications	Tumors of mice treated with PBS grew rapidly, to approximately 10 folds of their initial volume in the 25th day, whereas, tumors in the Fludarabine treatment group increased less than 5 folds. In SCID mice bearing RPMI 8226 cells, treatment with 40 mg/kg Fludarabine for 10 days resulted in a significant increase in the number of apoptotic cells.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
参考文献: [1]. Meng H, Yang C, Ni W, et al. Antitumor activity of fludarabine against human multiple myeloma in vitro and in vivo. Eur J Haematol, 2007, 79(6): 486-493.