| 名稱(chēng) | Ispinesib |
| 描述 | Ispinesib (SB-715992), a selective, effectvie and reversible inhibitor of kinesin spindle protein (KSP), is derived from quinazolinone, with antineoplastic properties. |
| 細(xì)胞實(shí)驗(yàn) | Cells are plated in log phase of growth in 96-well plates and treated with Ispinesib for 72 hours. Then, cell growth is measured using CellTiter-Glo, and luminescence is detected using BioTek FLx800. Data are analyzed and the IC50 value, defined as the drug concentration that results in 50% growth inhibition relative to control, is calculated.(Only for Reference) |
| 激酶實(shí)驗(yàn) | Steady-State Kinetic Analysis of Human KSP ATPase Activity and Inhibition by Ispinesib: Kinesin specificity analysis is carried out using a pyruvate kinase-lactate dehydrogenase detection system that couples the production of ADP to oxidation of NADH. Absorbance changes are monitored at 340 nm. Steady-state studies using nanomolar concentrations of KSP are performed using a sensitive fluorescence-based assay utilizing a pyruvate kinase, pyruvate oxidase, and horseradish peroxidase (HRP) coupled detection system that couples the generation of ADP to oxidation of Amplex Red to fluorescent resorufin. Generation of resorufin is monitored by fluorescence (λexcitation = 520 nm and λemission = 580 nm). Steady-state biochemical experiments are performed in PEM25 buffer [25 mM Pipes-K+ (pH 6.8), 2 mM MgCl2, 1 mM EGTA] supplemented with 10 μM paclitaxel for experiments involving microtubules. The IC50 for steady-state inhibition is determined at 500 μM ATP, 5 μM Microtubules, and 1 nM KSP in PEM25 buffer. Ki app (apparent inhibitor dissociation constant) values of Ispinesib are extracted from the dose-response curves, with explicit correction for enzyme concentration by using the Morrison equation. Inhibitor modality (e.g., competitive, noncompetitive, uncompetitive, or mixed) under steady-state conditions is determined by measuring the effect of inhibitor concentration on initial velocity as a function of substrate concentrations. Data are fit using equations in GraFit to velocity equations for the various modes of inhibition. |
| 體外活性 | 攜帶移植瘤的小鼠模型, Ispinesib（4.5-15 mg/kg）能夠抑制Colo205, Colo201, HT-29細(xì)胞生長(zhǎng).在小鼠實(shí)體瘤中,用Ispinesib處理（6 -10 mg/kg ）,Madison 109肺癌, M5076肉瘤,及L1210和P388白血病能夠被抑制.攜帶乳腺癌細(xì)胞MCF-7, HCC1954, MDA-MB-468,和KPL4移植瘤的小鼠中,Ispinesib（8-10 mg/kg ）抑制腫瘤生長(zhǎng). |
| 體內(nèi)活性 | 在PC-3前列腺癌細(xì)胞中, Ispinesib（5 nM 和 30 nM）通過(guò)調(diào)節(jié)信號(hào)的基因表達(dá)水平,抑制細(xì)胞增殖和誘導(dǎo)細(xì)胞凋亡。在乳腺癌細(xì)胞系中, Ispinesib（7.4 nM–600 nM）具有廣譜抑制活性。在腫瘤細(xì)胞系中（Colo205, Colo201, HT-29, M5076, Madison-109,和MX-1）,Ispinesib（IC50=1.2-9.5 nM） 具有很強(qiáng)細(xì)胞毒性。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | Ethanol : 95 mg/mL (183.73 mM), Sonication is recommended.
DMSO : 95 mg/mL (183.73 mM), Sonication is recommended.
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| 關(guān)鍵字 | SB715992 | SB 715992 | KSP (HsEg5) | Kinesin | Ispinesib | Inhibitor | inhibit | CK-0238273 | CK 0238273 | Apoptosis |
| 相關(guān)產(chǎn)品 | L-Glutamic acid | Cysteamine hydrochloride | Alginic acid | Flubendazole | 5-Fluorouracil | Stavudine | Dextran sulfate sodium salt (MW 4500-5500) | Tributyrin | Myricetin | L-Ascorbic acid sodium salt | L-Ascorbic acid | Sodium 4-phenylbutyrate |
| 相關(guān)庫(kù) | 抑制劑庫(kù) | 經(jīng)典已知活性庫(kù) | 抗癌活性化合物庫(kù) | 已知活性化合物庫(kù) | 抗結(jié)直腸癌化合物庫(kù) | 臨床失敗化合物庫(kù) | 抗衰老化合物庫(kù) | 高選擇性抑制劑庫(kù) | 臨床期小分子藥物庫(kù) | 藥物功能重定位化合物庫(kù) | 抗癌臨床化合物庫(kù) | 抗癌藥物庫(kù) |