切换导航

Irinotecan

现货
Catalog No.
A5133
Topoisomerase I抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
100mg
¥ 500.00
现货

电话: 021-55669583

邮箱: sales@apexbio.cn

全球经销商

Background

Irinotecan (CPT-11), a prodrug for treating metastatic colorectal cancer, is a topoisomerase I inhibitor for LoVo cells and HT-29 cells with IC50 of 15.8 μM and 5.17 μM, respectively [1].In vivo, Irinotecan is converted to SN-38, its most active metabolite, by carboxylesterase converting enzyme (CCE) [2].

In vitro: Irinotecan induced similar amounts of cleavable complexes in LoVocells and HT-29 cell lines with the IC50 of 15.8 μM and 5.17 μM, respectively [1].After addition of 157 mM irinotecan to plasma, SN-38 concentration showed linear increase during the first 60-min period, followed by a plateau.In the first 60 min, mean and standard deviation of the conversion rate were 515.9 ± 50.1 pmol/ml/h (n = 69), with a coefficient of variation of 0.097 [2]. Irinotecan (CPT-11) was significantly more active in SCLC than in NSCLCcelllines (P = 0.0036). CE activity appeared to be associated with higher sensitivity to CPT-11 in human lung cancercelllines and may partly explain the difference in the in vitro sensitivity to CPT-11 between SCLC and NSCLCcells [3].In vitro, the sensitivity to CPT-11 and SN-38 was highest in LS174T and COLO 320cells, intermediate in SW1398cellsand lowest in COLO 205 and WiDr cells. The activity of SN-38 was 130 to 570 times than CPT-11[4].

In vivo: In COLO 320 xenografts, Irinotecan induced a maximum growth inhibition of 92% [4].A single dose of Irinotecan significantly increased amounts of topoisomerase I covalently bound to DNA in stomach, duodenum, colon and liver. Concomitantly, the Irinotecan-treated group exihibited significantly higher amounts of DNA strand breaks in colon mucosa cells compared to the control group [5].

References:
[1].  Tobin P, Clarke S, Seale J P, et al. The in vitro metabolism of irinotecan (CPT‐11) by carboxylesterase and β‐glucuronidase in human colorectal tumours[J]. British journal of clinical pharmacology, 2006, 62(1): 122-129.
[2]. Shingyoji M, Takiguchi Y, Watanabe‐Uruma R, et al. In vitro conversion of irinotecan to SN‐38 in human plasma[J]. Cancer science, 2004, 95(6): 537-540.
[3]. van Ark-Otte J, Kedde M A, Van Der Vijgh W J, et al. Determinants of CPT-11 and SN-38 activities in human lung cancer cells[J]. British journal of cancer, 1998, 77(12): 2171.
[4]. Jansen W J M, Zwart B, Hulscher S T M, et al. CPT-11 in human colon-cancer cell lines and xenografts: characterization of cellular sensitivity determinants[J]. International journal of cancer, 1997, 70(3): 335-340.
[5]. Na Y S, Jung K A, Kim S M, et al. The histone deacetylase inhibitor PXD101 increases the efficacy of irinotecan in in vitro and in vivo colon cancer models[J]. Cancer chemotherapy and pharmacology, 2011, 68(2): 389-398.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt586.68
Cas No.97682-44-5
FormulaC33H38N4O6
Solubility>29.4mg/mL in DMSO
Chemical Name4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl [1,4'-bipiperidine]-1'-carboxylate
SDFDownload SDF
Canonical SMILESO=C(OC1)C(O)(CC)C2=C1C(N(CC3=C4N=C5C(C=C(OC(N6CCC(N7CCCCC7)CC6)=O)C=C5)=C3CC)C4=C2)=O
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

HT29,NMG64/84,COLO-357,MIA PaCa-2,PANC-1细胞

溶解方法

该化合物在DMSO中的溶解度大于29.4 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

0.1-1000 μg/ml,30 min

应用

在所有测试的细胞系中,Irinotecan显示浓度和时间依赖性的细胞毒性作用。在COLO-357、MIA PaCa-2和PANC-1细胞中,Irinotecan增加G0/G1期的细胞数量,并减少S-和G2期细胞数。在HT29和NMG 64/84细胞中,低浓度的Irinotecan增加G2期细胞数。

动物实验 [2]:

动物模型

ICR雄性小鼠

给药剂量

腹腔注射,100 mg/kg

应用

Irinotecan(100mg/kg,i.p.)注射后体重变化的时间过程表现出显著的给药时间依赖性差异(P <0.01)。在第3天和第4天之间注射Irinotecan(CPT-11)后,平均体重减轻最多。在1700小时后注射Irinotecan(CPT-11)后平均体重减轻程度最小。

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]. HOFMANN C, BUTTENSCHOEN K, STRAETER J, et al. Pre-clinical evaluation of the activity of irinotecan as a basis for regional chemotherapy[J]. Anticancer research, 2005, 25(2A): 795-804.

[2]. Ohdo S, Makinosumi T, Ishizaki T, et al. Cell cycle-dependent chronotoxicity of irinotecan hydrochloride in mice[J]. Journal of Pharmacology and Experimental Therapeutics, 1997, 283(3): 1383-1388.

质量控制

化学结构

Irinotecan