Ispinesib (SB-715992)
别名: CK0238273 中文名称：伊斯平斯
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Kiapp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
产品质控
Ispinesib (SB-715992)相关产品
| 相关产品 | GSK923295 SB743921 HCl Monastrol ARQ 621 | 点击展开 |
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| 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 |
相关信号通路图
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 | 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Kiapp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。 | ||
|---|---|---|---|
| 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 |
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| 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] |
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| 激酶实验 | 人类KSP ATP酶活性和Ispinesib抑制的稳定动力学分析 | |||
| 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Ki 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。 |
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| 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] |
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|---|---|---|
| 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 |
|---|---|---|---|---|---|
| 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 |
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) | |||
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体外溶解度 |
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 |
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体内溶解度 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 | ||||
实验计算
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）
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）
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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