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]。