Ispinesib (SB-715992)

别名: CK0238273 中文名称：伊斯平斯

目录号：S1452 Purity: 99.97%

Ispinesib (SB-715992, CK0238273)是一种有效的，特异性的，可逆kinesin spindle protein (KSP)抑制剂，无细胞试验中K_iapp为1.7 nM，对CENP-E， RabK6， MCAK， MKLP1，KHC和Kif1A没有抑制作用。Ispinesib可诱导有丝分裂阻滞和细胞的凋亡。

Ispinesib (SB-715992) Chemical Structure

CAS: 336113-53-2

规格	价格	库存
10mM (1mL in DMSO)	2170	现货
1mg	794.43	现货
10mg	2621.56	现货
50mg	7941.69	现货
200mg	20229.3	现货
1g	54873	现货
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产品质控

批次：纯度： 99.97%

99.97

Ispinesib (SB-715992)相关产品

相关靶点	Kinesin-12	点击展开
相关产品	GSK923295 SB743921 HCl Monastrol ARQ 621	点击展开
相关化合物库	激酶抑制剂库血管生成相关化合物库 TGF-beta/Smad信号通路库细胞骨架信号通路化合物库抗心血管疾病化合物库	点击展开

细胞实验数据示例

细胞系	实验类型	给药浓度	孵育时间	活性描述	文献信息
LXFS 538	Antitumor assay	6 mg/kg		Antitumor activity against human LXFS 538 cells xenografted in NMRI nu/nu mouse assessed as tumor regression at 6 mg/kg, ip measured on day 13	23394180
HCT116	Growth inhibition assay		72 hrs	Growth inhibition of human HCT116 cells after 72 hrs by MTS assay, IC50=0.0011μM	26396688
MCF7	Antiproliferative assay		48 hrs	Antiproliferative activity against human MCF7 cells after 48 hrs by MTT assay, IC50=1.3μM	24184776
HeLa	Antiproliferative assay		48 hrs	Antiproliferative activity against human HeLa cells after 48 hrs by MTT assay, IC50=1μM	24184776
NCI-H1299	Growth inhibition assay		72 hrs	Growth inhibition of human NCI-H1299 cells after 72 hrs by Alamar blue assay, GI50=0.082μM	23394180
BxPC3	Growth inhibition assay		72 hrs	Growth inhibition of human BxPC3 cells after 72 hrs by Alamar blue assay, GI50=0.08μM	23394180
PC3	Growth inhibition assay		72 hrs	Growth inhibition of human PC3 cells after 72 hrs by Alamar blue assay, GI50=0.05μM	23394180
HCT116	Growth inhibition assay		72 hrs	Growth inhibition of human HCT116 cells after 72 hrs by Alamar blue assay, GI50=0.025μM	23394180
LNCAP	Growth inhibition assay		72 hrs	Growth inhibition of human LNCAP cells after 72 hrs by Alamar blue assay, GI50=0.022μM	23394180
NCI-H1299	Antiproliferative assay		72 hrs	Antiproliferative activity against human NCI-H1299 cells after 72 hrs by Alamar blue assay, GI50=0.082μM	22248262
BxPC3	Antiproliferative assay		72 hrs	Antiproliferative activity against human BxPC3 cells after 72 hrs by Alamar blue assay, GI50=0.08μM	22248262
K562	Antiproliferative assay		72 hrs	Antiproliferative activity against human K562 cells after 72 hrs by Alamar blue assay, GI50=0.071μM	22248262
hTERT-HME1	Antiproliferative assay		72 hrs	Antiproliferative activity against human hTERT-HME1 cells after 72 hrs by Alamar blue assay, GI50=0.032μM	22248262
HCT116	Antiproliferative assay		72 hrs	Antiproliferative activity against human HCT116 cells after 72 hrs by Alamar blue assay, GI50=0.025μM	22248262
Rh30	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
RD	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
U-2 OS	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
Rh41	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
BT-37	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
OHS-50	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
BT-12	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
LAN-5	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
NB-EBc1	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
SK-N-MC	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
A673	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SJ-GBM2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
DAOY	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
TC32	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
Saos-2	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
SK-N-SH	qHTS assay			qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
点击查看更多细胞系数据

生物活性

产品描述

特性

Ispinesib是一种有效可逆的特定有丝分裂驱动蛋白(KSP)变构抑制剂。

靶点

KSP (HsEg5) ^[1]
(Cell-free assay)

1.7 nM(Ki app)

体外研究(In Vitro)
体外研究活性	Ispinesib 是有效可逆的特定KSP变构抑制剂，KSP与微管的结合性能，通过抑制ADP释放而不改变微管中KSP-ADP复合体的释放，而扰乱KSP的运动。^[1] Ispinesib作用于一系列肿瘤细胞系, 包括Colo205, Colo201, HT-29, M5076, Madison-109,和MX-1, IC50为1.2 nM 到 9.5 nM，具有很强细胞毒性。^[2] 15 nM 和 30 nM Ispinesib作用于PC-3前列腺癌细胞, 通过调节控制凋亡，细胞增殖，细胞周期，和信号的基因表达水平，如EGFR, p27, p15, 和IL-11，而抑制细胞增殖和诱导凋亡。^[3] 7.4 nM–600 nM Ispinesib 作用于一组53种乳腺癌细胞系,具有广谱抑制活性。150 nM Ispinesib 作用于BT-474 和MDA-MB-468细胞,诱导凋亡, 提高凋亡细胞比例，降低抗凋亡的Bcl-XL水平,和提高促凋亡的Bax和Bid 水平。^[4]
激酶实验	人类KSP ATP酶活性和Ispinesib抑制的稳定动力学分析
激酶实验	使用丙酮酸激酶-乳酸脱氢酶检测体系进行驱动蛋白的特异性分析，伴随着NADH氧化产生ADP。在340 nm处检测吸光度的变化。使用纳摩尔浓度KSP进行稳态研究，使用一个敏感的荧光为基础的检测系统，利用丙酮酸激酶，丙酮酸氧化酶，辣根过氧化物酶（HRP）耦合的检测体系，伴随着Amplex红色荧光试剂氧化为试卤灵而生成ADP。通过荧光检测产生的试卤灵。在含10 µM 紫杉醇的PEM25 buffer [25 mM Pipes-K⁺ (pH 6.8), 2 mM MgCl₂, 1 mM EGTA]中进行稳态生化试验。在含500 µM ATP, 5 µM 微管,和1 nM KSP的PEM25 buffer中测定抑制稳定的IC50值。通过剂量-反应曲线获得Ispinesib的K_i app(明显的抑制剂解离常数)值, 通过使用Morrison方程明确纠正酶浓度。在稳态情况下测定抑制剂形态（竞争性，非竞争性，无竞争力的，或者混合生物）。
细胞实验	细胞系	Breast 乳腺癌细胞，包括MCF-7, HCC1954, MDA-MB-468,和KPL4
	浓度	0.085 nM-33 μM
	孵育时间	72小时
	方法	指数生长期细胞接种在96孔板上，用Ispinesib处理72小时。然后使用CellTiter-Glo测量细胞生长, 并使用BioTek FLx800测定荧光值。分析数据，计算IC50值。

体内研究(In Vivo)
体内研究活性	Ispinesib按4.5 mg/kg-15 mg/kg剂量作用于携带移植瘤的小鼠模型，有效抑制Colo205, Colo201, HT-29细胞，但是不抑制MX-1细胞。SB-715992按6 mg/kg-10 mg/kg剂量处理，也抑制小鼠实体瘤，包括 Madison 109 肺癌, M5076肉瘤,及L1210和P388白血病。^[2] Ispinesib 按8 mg/kg-10 mg/kg剂量作用于携带乳腺癌细胞MCF-7, HCC1954, MDA-MB-468,和KPL4移植瘤的小鼠,抑制肿瘤生长。^[4]
动物实验	Animal Models	携带MCF7, KPL4,和HCC1954细胞的(nu/nu)裸鼠模型，携带MDA-MB-468 细胞的SCID小鼠模型
	Dosages	10 mg/kg作用于裸鼠，8 mg/kg作用于SCID 鼠
	Administration	3倍剂量腹腔注射，每隔四天进行一次

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
临床试验信息 (data from https://clinicaltrials.gov, updated on 2024-05-22)
NCT00607841	Terminated	Breast Neoplasms	Cytokinetics	December 2007	Phase 1
NCT00354250	Completed	Recurrent Renal Cell Cancer\|Stage III Renal Cell Cancer\|Stage IV Renal Cell Cancer	National Cancer Institute (NCI)	May 2006	Phase 2
NCT00097409	Completed	Ovarian Cancer	GlaxoSmithKline	December 2004	Phase 2
NCT00119171	Completed	Solid Tumor Cancer	GlaxoSmithKline	November 2004	Phase 1

参考文献
[1] Lad L, et al. Biochemistry, 2008, 47(11), 3576-3585. [2] Johnson RK, et al. Proc Am Assoc Cancer Res, 2002, 43, 269. [3] Davis DA, et al. BMC Cancer, 2006, 6, 22. [4] Purcell JW, et al. Clin Cancer Res, 2010, 16(2), 566-576. + 展开

参考文献

[4] Purcell JW, et al. Clin Cancer Res, 2010, 16(2), 566-576.

+ 展开

化学信息&溶解度

分子量	517.06	分子式	C₃₀H₃₃ClN₄O₂
CAS号	336113-53-2	SDF	Download Ispinesib (SB-715992) SDF
Smiles	CC1=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
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1年-80°C溶于溶剂
储存条件(自收到货起)	3年-20°C粉状	储备液保存和期限建议分装储备液，避免反复冻融！	1个月-20°C溶于溶剂

体外溶解度
批次：

DMSO : 103 mg/mL ( (199.2 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Ethanol : 103 mg/mL (199.2 mM)

Water : Insoluble

DMSO : 103 mg/mL ( (199.2 mM) ；DMSO吸湿会降低化合物溶解度，请使用新开封DMSO)

Ethanol : 103 mg/mL (199.2 mM)

Water : Insoluble

摩尔浓度计算器

体内溶解配方批次：现配现用，请按从左到右的顺序依次添加，澄清后再加入下一溶剂				动物体内配方计算器
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。
澄清溶液	2%DMSO 1 Corn oil 该配方已经过Selleck实验室实测。如果上述溶解方案不能满足您的需求，可联系Selleck销售提供定制化测试。	4.000mg/ml (7.74mM)	以 1 mL 工作液为例，取20μL200mg/ml的澄清DMSO储备液加到980μL玉米油中，混合均匀。工作液请现配现用！
均匀悬浊液	CMC-NA	≥5mg/ml	以 1 mL 工作液为例，取 5 mg该产品加到 1 ml CMC-NA 溶液中，混合均匀，即可得工作液浓度为 5 mg/ml的均匀悬浊液。

实验计算

摩尔浓度计算器

质量	浓度	体积	分子量
=	×	×

稀释计算器分子量计算器

动物体内配方计算器（澄清溶液）

第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量）

给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 μL 动物数量只

第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方）

% DMSO + % + % Tween 80 + % ddH2O

%DMSO+ %

计算结果：

工作液浓度： mg/ml；

DMSO母液配制方法： mg 药物溶于μL DMSO溶液（母液浓度mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）；

体内配方配制方法：取μL DMSO母液，加入μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入μL ddH₂O，混匀澄清。

体内配方配制方法：取μL DMSO母液，加入μL Corn oil，混匀澄清。

注意：1. 首先保证母液是澄清的；
2.一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。

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