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Ispinesib

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Chemical Structure| 336113-53-2 同义名 : 伊匹尼塞 ;SB-715992;CK0238273
CAS号 : 336113-53-2
货号 : A279561
分子式 : C30H33ClN4O2
纯度 : 99%+
分子量 : 517.062
MDL号 : MFCD22628831
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(232.08 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • Kinesin

    KSP (HsEg5), Ki app:1.7 nM
描述 Kinesins are motor proteins that have various of cellular physiologies, including mitosis, meiosis and cellular cargo transportation[1]. Ispinesib is a highly specific inhibitor of the kinesin spindle protein (KSP) with a median IC50 value of 5 nM[2].
The MDA-MB-468 cells (sensitive to ispinesib) and BT-474 cells(not sensitive to ispinesib) were treated with 150 nmol/L ispinesib and the expression of cell cycle markers (cyclin A, cyclin B and cyclin E) and apoptotic proteins (Bax, Bid, phospho-Bcl2, Bcl2 and Bcl-XL) were analyzed by western blotting at 0, 6, 16 and 48 hours. The expression of proteins Bax and Bid was higher in MDA-MB-468 cells and antiapoptitic protein Bcl-XL was lower. The marker of mitosis cyclin B was increased as the time increased in MDA-MB-468 cells but not in BT-474 cells. The cyclin E also increased after the ispinesib treatment on MDA-MB-468 cells[3].
CB17SC-M scid -/- female mice and BALB/c nu/nu mice with tumors xenografts were intraperitoneally administered Ispinesib (5 or 10 mg/kg) every 4 days for 3 doses repeated at day 21. Ispinesib could significantly delay the tumor growth in 88% and had intermediate 21% of solid tumor xenografts[4].
作用机制 The ability of KSP to bind to microtubules and the movement is changed and inhibited by ispinesib through preventing ADP release without inhibiting the release of the KSP-ADP complex from the microtubule[5].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human BxPC3 cells Growth inhibition assay 72 h Growth inhibition of human BxPC3 cells after 72 hrs by Alamar blue assay, GI50=0.08 μM 23394180
human BxPC3 cells Proliferation assay 72 h Antiproliferative activity against human BxPC3 cells after 72 hrs by Alamar blue assay, GI50=0.08 μM 22248262
human HCT116 cells Growth inhibition assay 72 h Growth inhibition of human HCT116 cells after 72 hrs by MTS assay, IC50=1.1 nM 26396688
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00169520 Solid Tumor Cancer Phase 1 Completed - United Kingdom ... 展开 >> GSK Investigational Site Oxford, Oxfordshire, United Kingdom, OX2 6PD GSK Investigational Site London, United Kingdom, SW3 6JJ 收起 <<
NCT00607841 Breast Neoplasms Phase 1 Phase 2 Completed - Peru ... 展开 >> Hospital Nacional Alberto Sabogal Sologúren Lima, Peru Hospital Nacional Edgardo Rebagliati Martins Lima, Peru Instituto Nacional de Enfermedades Neoplásicas Lima, Peru 收起 <<
NCT00103311 - Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.93mL

0.39mL

0.19mL

9.67mL

1.93mL

0.97mL

19.34mL

3.87mL

1.93mL
参考文献

[1]Endow SA, Kull FJ, Liu H. Kinesins at a glance. J Cell Sci. 2010;123(Pt 20):3420-4.

[2]Sheth PR, Basso A, et al. Thermodynamics of nucleotide and inhibitor binding to wild-type and ispinesib-resistant forms of human kinesin spindle protein. Biochemistry. 2009;48(46):11045-55.

[3]Purcell JW, Davis J, et al. Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer. Clin Cancer Res. 2010;16(2):566-76.

[4]Carol H, Lock R, 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):1255-63.

[5]Lad L, Luo L, et al. Mechanism of inhibition of human KSP by ispinesib. Biochemistry. 2008;47(11):3576-85.