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RITA (NSC 652287)

现货
Catalog No.
A4202
Mdm2-p53和p53泛素化抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 790.00
现货
5mg
¥ 800.00
现货
10mg
¥ 1,300.00
现货
25mg
¥ 2,000.00
现货
50mg
¥ 3,500.00
现货

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Background

IC50: 2 nM and 20 nM for A-498 and TK-10, respectively

A series of naturally occurring and synthetic compounds containing one or more thiophene moieties have been tested in the NCI Anticancer Drug Screen and have demonstrated differential antiproliferative activity. Thiophene derivatives as a class exhibit very similar patterns of differential sensitivity, the molecular basis for which is not clear. The compound 2,5-bis(5-hydroxymethyl-2-thienyl) furan (NSC 652287), is the most potent thiophene derivative and has been selected as the lead compound for mechanistic studies.

In vitro: A number of cell lines showed a striking differential sensitivity to NSC 652287 when compared with the other cell lines in the panel, with GI50 values of 10–60 nM. The compound was found to decrease the initial number of cells by 50% (LC50) at a concentration of 100 nM in the A-498 cell line, compared with ~100 mM for the majority of the tumor cell lines. The A-498 and TK-10 cell lines were particularly sensitive to NSC 652287-induced cytotoxicity compared with ACHN and UO-31 cell lines [1].

In vivo: NSC 652287 was evaluated against A-498 tumor cell xenografts grown subcutaneously in nude mice. When NSC 652287 was administered twice a day, all three doses resulted in complete tumor regression in 100% of the treated mice by the end of the third treatment period. The tumors did not regrow during the remaining 40 days of the study, and no gross evidence of toxicity was observed. Studies with xenografts derived from other sensitive cell lines including the renal CAKI-1, melanoma UACC-257, ovarian OVCAR-5, and colon HCC-2998, showed moderate or minimal in vivo activity [2].

Clinical trials: Currenlty no clinical data are available.

Reference:
[1] Rivera MI, Stinson SF, Vistica DT, Jorden JL, Kenney S, Sausville EA.   Selective toxicity of the tricyclic thiophene NSC 652287 in renal carcinoma cell lines: differential accumulation and metabolism. Biochem Pharmacol. 1999;57(11):1283-95.

Chemical Properties

StorageStore at -20°C
M.Wt292.4
Cas No.213261-59-7
FormulaC14H12O3S2
Solubility≥14.6 mg/mL in DMSO, ≥9.84 mg/mL in EtOH with ultrasonic and warming, <2.3 mg/mL in H2O
Chemical Name[5-[5-[5-(hydroxymethyl)thiophen-2-yl]furan-2-yl]thiophen-2-yl]methanol
SDFDownload SDF
Canonical SMILESC1=C(SC(=C1)C2=CC=C(O2)C3=CC=C(S3)CO)CO
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

人肾肿瘤细胞系

溶解方法

该化合物在DMSO中的溶解度大于14.6 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

48小时

应用

NSC 652287(48小时)抑制肿瘤细胞系的细胞生长,GI50值为10-60 nM。A-498和TK-10细胞系对NSC 652287诱导的细胞毒性特别敏感,IC50值分别为2 nM和20 nM。

动物实验 [1,2]:

动物模型

携带A-498肿瘤细胞异种移植物的裸鼠,HCT116肿瘤异种移植小鼠模型

给药剂量

静脉注射,间隔7小时,每4天,持续12天

应用

在小鼠的第三个治疗期结束时,44.5 mg/kg、66.7 mg/kg及100 mg/kg剂量的NSC 652287引起所有小鼠中的肿瘤完全消退。在小鼠中,腹膜内给药NSC 652287后耐受性良好,在1个月内,剂量高达10 mg/kg时没有引起体重减轻。注射5次0.1 mg/kg的NSC 652287抑制40%的HCT116肿瘤生长。NSC 652287(1或10 mg/kg)显示出强的抗肿瘤活性。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Rivera M I, Stinson S F, Vistica D T, et al. Selective toxicity of the tricyclic thiophene NSC 652287 in renal carcinoma cell lines: differential accumulation and metabolism[J]. Biochemical pharmacology, 1999, 57(11): 1283-1295.

[2]. Issaeva N, Bozko P, Enge M, et al. Small molecule RITA binds to p53, blocks p53-HDM-2 interaction and activates p53 function in tumors[J]. Nature medicine, 2004, 10(12): 1321.

生物活性

描述 RITA (NSC 652287)是DNA蛋白和DNA DNA交叉连接的一种诱导物,是MDM2-p53的抑制剂,作用靶点是p53。
靶点 DNA cross-links (A498 cells) DNA cross-links (TK-10 cells)        
IC50 2 nM 20 nM        

质量控制

化学结构

NSC 652287

相关生物数据

NSC 652287

相关生物数据

NSC 652287