基本信息

技术规格

物性(参考值)

基本信息

产品描述

Combretastatin A4 是一种以 microtubule 为靶点的试剂，其与β-微管蛋白结合，Kd 为 0.4 μM。Phase 3。

靶点（IC50 & Targe）

Tubulin β,0.4μM(Kd)

体外研究

Combretastatin A4抑制MDA-MB-231，A549，Hela，HL-60，SF295，HCT-8，MDA-MB435，PC3M，OVCAR-8，NCI-H358M，和淋巴细胞的生长，IC50分别为2.8，3.8，0.9，2.1，6.2，5.3，7.9，4.7，0.37，8，和3.2 nM。[1] [2]1 μM Combretastatin A4抑制35%微管蛋白聚合，10 μM几乎完全阻断微管蛋白聚合。Combretastatin A4表现出高的相对结合能力，达到秋水仙碱结合力的78%。[1]

体内研究

在NT2和MDA-MB-231乳腺肿瘤模型中，Combretastatin A4 (100 mg/kg, i.p.)诱导脂质R1显著减少，并通过电子顺磁共振(EPR)血氧定量法测得pO2下降。[2] Combretastatin A4 (100 mg/kg, i.p.)显著减少雄性NMRI小鼠的Ktrans。[3]

激酶实验

使用 LC-MS/MS 的竞争性结合试验:

Colchicine (1.2 μ M)与微管蛋白(1.3 mg/mL)在培养缓冲液(80 mM PIPES，2.0 mM MgCl2，0.5 mM EGTA，pH 6.9)中于37℃下培养1小时。使用不同浓度(0.1− 125 μ M)的Combretastatin A4与原本结合微管蛋白的colchicine竞争。培育后，得到滤液。类似物抑制秋水仙碱结合的能力表示为不存在任何竞争物的对照组的百分比。

细胞实验

Cell lines: MDA-MB-231，A549，和 Hela 细胞

Concentrations: ～3.8 nM

Incubation Time: 72 h

Method: MDA-MB-231，A549，和HeLa细胞在DMEM培养基(115 units/mL 青霉素G，115 μg/mL 链霉素，和10%胎牛血清)中生长。细胞(5000 细胞/孔)接种于包含50 μL生长培养基的96孔板，培养24小时。移除培养基后，将100 μL包含不同浓度单个类似化合物的新鲜培养基加入到每个孔中，在37 ℃下培养72小时。培养24小时后，细胞中增补50 μL溶于DMSO(每个制剂中少于0.25%)的类似化合物。培养72小时后，加入20 μL刃天青培养2小时，然后在560 nm (激发波长)和590 nm (发射波长)下使用Victor微量滴定板荧光剂记录荧光。对照组为用最大量DMSO (0.25%)处理的细胞，活性为100%，IC50定义为与对照组相比，抑制50%细胞增殖的化合物浓度。

(Only for Reference)

动物实验

Animal Models: 负荷 NT2 和 MDA-MB-231肿瘤的 FVB/N或裸的NMRI雄性小鼠

Formulation: DMSO

Dosages: 100 mg/kg

Administration: i.p.

(Only for Reference)

参考文献

[1] Zheng S, et al. J Med Chem. 2014, 57(8), 3369-3381.

[2] Colliez F, et al. Magn Reson Med. 2015, doi: 10.1002/mrm.25642.

[3] Fruytier AC, et al. NMR Biomed. 2014, 27(11), 1403-1412.

安全信息

图形或危害标志
提示语	Danger
危险说明	H301 H311 H318 H331
防范说明	P261 P280 P301+P310 P305+P351+P338 P311
UN号码	2811
危险分类	6.1
包装等级	III
WGK	2

产品说明

一般描述

考布他汀A4属于秋水仙碱类。

应用

考布他汀A4已被用于：

• 作为抗微管剂用于确定G2/M期异柠檬酸脱氢酶(IDH1和IDH2)蛋白的作用
• 评估联苯CA4衍生物在2D和3D癌细胞和非癌细胞模型中的的抗增生和促凋亡特性
• 作为微管抑制剂用于研究其对猪蛔虫L3幼虫的作用

包装

5, 25 mg in glass bottle

生化/生理作用

考布他汀A4是一种强效的微管靶向剂。
Combretastatin A4是一种靶向肿瘤血管以抑制血管生成的血管分裂剂(VDA)。它在β-微管蛋白的秋水仙碱结合位点抑制微管蛋白聚合。它通过抑制人胃细胞中的AKT功能而具有抗肿瘤活性。被抑制的 AKT 激活引起细胞增殖下降，细胞周期停滞，在体外 迁移/侵袭和 体内 转移能力降低 。Combretastatin A4 是一种天然二苯乙烯类苯酚。

基本信息

产品性质

安全信息

象形图
警示用语：	Danger
危险声明	H301 + H311 + H331 - H318
预防措施声明	P261 - P280 - P301 + P310 - P302 + P352 + P312 - P304 + P340 + P311 - P305 + P351 + P338
危险分类	Acute Tox. 3 Dermal - Acute Tox. 3 Inhalation - Acute Tox. 3 Oral - Eye Dam. 1
储存分类代码	6.1C - Combustible, acute toxic Cat.3 / toxic compounds or compounds which causing chronic effects
WGK	WGK 2
闪点(F)	Not applicable
闪点(C)	Not applicable
个人防护装备	Eyeshields, Faceshields, Gloves, type P2 (EN 143) respirator cartridges

产品说明

一般描述

A synthetic Combretum caffrum-derived cell-permeable stilbenoid phenol that competes with colchicine (Cat No. 234115) tubulin binding (by 96.4% at equal molar concentration; Ki = 1.1 µM) and interferes with tubulin polymerization (IC₅₀ = 2-3 µM) as well as cellular microtubule assembly. In addition to its antimitotic and in vitro cancer growth inhibition activity (IC₅₀ = 7 nM in L1210 cultures), CA4 also acts as an antivascular agent and effectively induces tumor cell necrosis in vivo by targeting endothelial cytoskeleton.
A synthetic Combretum caffrum-derived cell-permeable stilbenoid phenol that competes with colchicine (Cat. No. 234115) tubulin binding (by 96.4% at equal molar concentration; Ki = 1.1 µM) and interferes with tubulin polymerization (IC₅₀ = 2-3 µM) as well as cellular microtubule assembly. In addition to its antimitotic and in vitro cancer growth inhibition activity (IC₅₀ = 7 nM in L1210 cultures), CA4 also acts as an antivascular agent and effectively induces tumor cell necrosis in vivo by targeting endothelial cytoskeleton.

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

重悬

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

其他说明

Tron, G.C., et al. 2006. J. Med. Chem.49, 3033.
Griggs, J., et al. 2001. Lancet Oncol.2, 82.
Pettit, G.R., et al. 1989. Experientia45, 209.
Lin, C.M., et al. 1988. Mol. Pharmacol.34, 200.

法律信息

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

基本信息

产品性质

安全信息

象形图
警示用语：	Danger
危险声明	H301 + H311 + H331 - H318
预防措施声明	P261 - P280 - P301 + P310 - P302 + P352 + P312 - P304 + P340 + P311 - P305 + P351 + P338
危险分类	Acute Tox. 3 Inhalation - Acute Tox. 3 Oral - Dermal
储存分类代码	6.1C - Combustible, acute toxic Cat.3 / toxic compounds or compounds which causing chronic effects
WGK	WGK 2
闪点(F)	Not applicable
闪点(C)	Not applicable

基本信息

安全信息

图形或危害标志
危险性说明	H301 + H311 + H331: Toxic if swallowed , in contact with skin or if inhaled H315: Causes skin irritation. H318: Causes serious eye damage. H335: May cause respiratory irritation.
防范说明	P233: Keep container tightly closed. P260: Do not breathe . P261: Avoid breathing . P264: Wash hands thoroughly after handling. P270: Do not eat, drink or smoke when using this product. P271: Use only outdoors or in a well-ventilated area. P280: Wear . P301 + P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. P302 + P352: IF ON SKIN: Wash with plenty of soap and water. P304: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.. P304 + P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P305 + P351 + P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P310: Immediately call a POISON CENTER or doctor/physician. P311: Call a POISON CENTER or doctor/physician. P312: Call a POISON CENTER or doctor/physician if you feel unwell. P321: Specific treatment (see relevant procedures. on this label). P322: Specific measures (see . on this label). P330: Rinse mouth. P332 + P313: If skin irritation occurs: Get medical advice/ attention. P340: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P361: Remove/Take off immediately all contaminated clothing. P362: Take off contaminated clothing and wash before reuse. P363: Wash contaminated clothing before reuse. P403: Store in a well-ventilated place. P403 + P233: Store in a well-ventilated place. Keep container tightly closed. P405: Store locked up. P501: Dispose of contents/container to in accordance with local regulation .