BI6727(Volasertib)
(Synonyms: 伏拉塞替; BI 6727) 目录号 : GC11224
BI6727(Volasertib)是一种口服ATP竞争性Polo样激酶（PLK）抑制剂，可强效抑制PLK1、PLK2和PLK3活性，IC50值分别为0.87nM、5nM和56nM。
Cas No.:755038-65-4
Sample solution is provided at 25 µL, 10mM.
BI6727(Volasertib) is an orally ATP-competitive polo-like kinase (PLK) inhibitor and potently inhibits PLK1, PLK2 and PLK3 with IC50 values of 0.87nM, 5nM and 56nM, respectively[1]. BI6727 has been widely used in various cancer cell lines and cancer xenograft models as an anti-cancer agent[2].
In vitro, BI6727 treatment for 4 days significantly inhibited the viability of anaplastic thyroid cancer (ATC) cell lines, with the IC50 values of 22.7nM for 8505C cells and 51.2nM for KAT18 cells, respectively[3]. Treatment of HeLa cells with 0.03μM BI6727 for 48 hours significantly inhibited cell growth, induced cell cycle arrest in G2/M phase, and cell apoptosis, and decreased the protein expression of PLK1 substrates survivin and wee1[4]. Treatment of A375 cells with 100nM BI6727 for 24h resulted in the decreased growth, viability, and colony-forming survival as well as increased apoptosis[5].
In vivo, BI6727 treatment (20mg/kg/week; i.p.) for 5 weeks significantly suppressed tumor volume and weight in the H526 cell xenograft mouse model without changing body weight[6]. Intravenous injection of BI6727 at a dose of 40mg/kg once weekly for 12 weeks significantly reduced tumor volume and prolonged mouse survival in MV-4-11 tumor-bearing nude mice[7].
References:
[1] Rudolph D, Steegmaier M, Hoffmann M, et al. BI 6727, a Polo-like kinase inhibitor with improved pharmacokinetic profile and broad antitumor activity[J]. Clinical cancer research, 2009, 15(9): 3094-3102.
[2] Gjertsen B T, Schöffski P. Discovery and development of the Polo-like kinase inhibitor volasertib in cancer therapy[J]. Leukemia, 2015, 29(1): 11-19.
[3] Lin S F, Yeh C N, Huang Y T, et al. Therapeutic inhibition of polo‐like kinases in anaplastic thyroid cancer[J]. Cancer Science, 2021, 112(2): 803-814.
[4] Xie F F, Pan S S, Ou R Y, et al. Volasertib suppresses tumor growth and potentiates the activity of cisplatin in cervical cancer[J]. American journal of cancer research, 2015, 5(12): 3548.
[5] Cholewa B D, Ndiaye M A, Huang W, et al. Small molecule inhibition of polo-like kinase 1 by volasertib (BI 6727) causes significant melanoma growth delay and regression in vivo[J]. Cancer letters, 2017, 385: 179-187.
[6] Zhang G, Pannucci A, Ivanov A A, et al. Polo-like Kinase 1 Inhibitors Demonstrate In Vitro and In Vivo Efficacy in Preclinical Models of Small Cell Lung Cancer[J]. Cancers, 2025, 17(3): 446.
[7] Rudolph D, Impagnatiello M A, Blaukopf C, et al. Efficacy and mechanism of action of volasertib, a potent and selective inhibitor of Polo-like kinases, in preclinical models of acute myeloid leukemia[J]. The Journal of pharmacology and experimental therapeutics, 2015, 352(3): 579-589.
BI6727(Volasertib)是一种口服ATP竞争性Polo样激酶（PLK）抑制剂，可强效抑制PLK1、PLK2和PLK3活性，IC50值分别为0.87nM、5nM和56nM[1]。BI6727作为抗癌剂已广泛应用于多种癌细胞系和癌症异种移植模型的研究[2]。
在体外，BI6727处理4天可显著抑制间变性甲状腺癌（ATC）细胞系活力，对8505C和KAT18细胞的IC50值分别为22.7nM和51.2nM[3]。0.03μM的BI6727处理HeLa细胞48小时能显著抑制细胞生长，诱导G2/M期细胞周期阻滞和凋亡，并降低PLK1底物survivin和wee1蛋白表达[4]。100nM的BI6727处理A375细胞24小时可抑制细胞生长、活力及克隆形成能力，同时促进凋亡[5]。
在体内，H526细胞异种移植小鼠模型每周腹腔注射BI6727（20mg/kg；持续5周）可显著抑制肿瘤体积和重量，且不影响体重[6]。MV-4-11荷瘤裸鼠每周静脉注射40mg/kg剂量的BI6727（持续12周）能显著减小肿瘤体积并延长生存期[7]。
| Cell experiment [1]: | |
Cell lines | A375 cells |
Preparation Method | A375 cells (1×105) were seeded in 6-well tissue culture dishes and treated with BI6727 (1, 10, 25, 50, and 100nM) for 24h. After treatment, the cells were trypsinized for 5min and then transferred to a 5mL centrifuge tube containing medium. The cells were centrifuged at 1000RPM for 2min, the supernatant was aspirated, and the cells were resuspended in 4% paraformaldehyde for fixation before flow cytometry analysis. |
Reaction Conditions | 1, 10, 25, 50, and 100nM; 24h |
Applications | BI6727 significantly induced apoptosis of A375 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Athymic (nu/nu) mice |
Preparation Method | Six-week-old athymic (nu/nu) mice were housed in microisolation cages under pathogen-free conditions and fed laboratory food and water ad libitum. H526 cells (1×107) suspended in serum-free medium were mixed with Matrigel solution and injected subcutaneously into the flank region of mice. Subcutaneous tumor growth was measured until the tumor size reached approximately 100mm3. Tumor-bearing mice were matched by body weight and tumor volume and randomly assigned to each treatment group, with 6-8 mice in each group. Mice were treated with the following compounds: BI6727 (20mg/kg; weekly intraperitoneal injection), cisplatin (3mg/kg; weekly i.p.), irinotecan (25mg/kg; weekly i.p.), and cisplatin (3mg/kg; weekly i.p.). Tumor volume (V = 1/2ab2, where "a" and "b" represent tumor length and width, respectively) and body weight were monitored twice weekly. At the end of the experiment, subcutaneous tumors were removed and weighed. |
Dosage form | 20mg/kg/week; for 5 weeks; i.p. |
Applications | BI6727 treatment significantly suppressed tumor volume and weight without changing the body weight of mice. |
References: | |
| Cas No. | 755038-65-4 | SDF | |
| 别名 | 伏拉塞替; BI 6727 | ||
| 化学名 | N-[4-[4-(cyclopropylmethyl)piperazin-1-yl]cyclohexyl]-4-[[(7R)-7-ethyl-5-methyl-6-oxo-8-propan-2-yl-7H-pteridin-2-yl]amino]-3-methoxybenzamide | ||
| Canonical SMILES | CCC1C(=O)N(C2=CN=C(N=C2N1C(C)C)NC3=C(C=C(C=C3)C(=O)NC4CCC(CC4)N5CCN(CC5)CC6CC6)OC)C | ||
| 分子式 | C34H50N8O3 | 分子量 | 618.83 |
| 溶解度 | ≥ 10.3mg/mL in DMSO | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.616 mL | 8.0798 mL | 16.1595 mL |
| 5 mM | 0.3232 mL | 1.616 mL | 3.2319 mL |
| 10 mM | 0.1616 mL | 0.808 mL | 1.616 mL |
| 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 | ul | |
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GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet