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Ispinesib (SB-715992)

现货
Catalog No.
A5343
驱动蛋白纺锤体蛋白(KSP)抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,820.00
现货
5mg
¥ 1,250.00
现货
10mg
¥ 1,900.00
现货
50mg
¥ 6,800.00
现货
100mg
¥ 9,800.00
现货

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Background

Ispinesib (SB-715992) is a selective inhibitor of KSP with IC50 value of 0.5 nM [1].

Kinesin spindle protein (KSP) is a kinesin motor protein and plays an important role in the formation of a bipolar mitotic spindle and cell cycle progression through mitosis. It has been shown that abnormal expression of KSP is correlated with a variety of human cancers and its inhibitors may be a promising anticancer agent [2] [3].

Ispinesib (SB-715992) is a potent KSP inhibitor and often combines with chemotherapy drugs to tumor treatment. When tested with a panel of 23 tumor cell lines, Ispinesib (SB-715992) treatment showed high activity to inhibit KSP in most of the cell lines while only Rh18 having an IC50 value greater than 1 μM (median IC50=4.1 nM, maximum IC50=0.5 nM) by using PPTP method [1]. In a panel of 53 breast cell lines, Ispinesib (SB-715992) exhibits broad antiproliferative activity and up-regulated the expression of both mitotic and apoptotic markers in MDA-MB-468 cell line [2]. When tested with PC-3 cells, Ispinesib (SB-715992) treatment inhibits cell proliferation, inducs cell apoptosis and up-regulated the expressions of genes that related to the control of cell proliferation, cell cycle, cell signaling pathways and apoptosis [3].

In mouse model with 26 tumor cells subcutaneous xenograft, administration of Ispinesib (SB-715992) inducs markedly tumor growth delay with the percent of 88% (23/26) and maintained completed response (CR) in the rhaboid tumor, Wilms tumor and Ewing sarcoma xenograft mouse model [1].

References:
[1].  Carol, H., et al., Initial testing (stage 1) of the kinesin spindle protein inhibitor ispinesib by the pediatric preclinical testing program. Pediatr Blood Cancer, 2009. 53(7): p. 1255-63.
[2].  Purcell, J.W., et al., Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer. Clin Cancer Res, 2010. 16(2): p. 566-76.
[3].  Davis, D.A., et al., Increased therapeutic potential of an experimental anti-mitotic inhibitor SB715992 by genistein in PC-3 human prostate cancer cell line. BMC Cancer, 2006. 6: p. 22.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt517.06
Cas No.336113-53-2
FormulaC30H33ClN4O2
Solubility≥25.85mg/mL in DMSO, ≥48.4 mg/mL in EtOH, <2.47 mg/mL in H2O
Chemical NameN-(3-aminopropyl)-N-[(1R)-1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-methylpropyl]-4-methylbenzamide
SDFDownload SDF
Canonical SMILESCC1=CC=C(C=C1)C(=O)N(CCCN)C(C2=NC3=C(C=CC(=C3)Cl)C(=O)N2CC4=CC=CC=C4)C(C)C
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

BT-474、MD A-MB-468细胞系

制备方法

该化合物在DMSO中的溶解度大于10 mM,若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

72 h,GI50 = 45 nM (BT-474),GI50 = 19 nM (MD A-MB-468)

实验结果

用浓度增加的ispinesib处理细胞,并根据将生长减少50%所需的药物浓度进行分级。对于BT-474和MDA-MB-468细胞系的GI50值分别为45 nM和19 nM。

动物实验[1]:

动物模型

Nude nu/nu小鼠, SCID小鼠

给药剂量

8 mg/kg (SCID),10 mg/kg (nude),腹腔注射

实验结果

在MDA-MB-468肿瘤异种移植物的小鼠中,腹膜注射ispinesib(SCID,8 mg/kg,nude,10 mg/kg),其MTD的最佳计划是q4d×3。体外最敏感细胞系三阴性异种移植模型MDA-MB-468表现出最大的体内ispinesib敏感性。在ispinesib治疗中,MDA-MB-468肿瘤在所有小鼠中完全消退,在研究结束时和在30天后各评分为TFS。

注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1] Purcell J W, Davis J, Reddy M, et al. Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer[J]. Clinical Cancer Research, 2010, 16(2): 566-576.

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