Volasertib (BI6727)

製品コードS2235 バッチS223509

印刷

化学情報

Chemical Structure Synonyms BI 6727 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C34H50N8O3
分子量 618.81 CAS No. 755038-65-4
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 20 mg/mL (32.32 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Volasertib is a highly potent Plk1 inhibitor with IC50 of 0.87 nM in a cell-free assay. It shows 6- and 65-fold greater selectivity against Plk2 and Plk3. Volasertib induces cell cycle arrest and apoptosis in various cancer cells. Phase 3.
in vitro

Like BI2536, BI6727 is an ATP-competitive kinase inhibitor from the dihydropteridinone class of compounds. In addition to Plk1, this compound also potently inhibits two closely related kinases Plk2 and Plk3 with IC50 of 5 nM and 56 nM, respectively. This chemical at concentrations up to 10 μM displays no inhibitory activity against a panel of >50 other kinases. It inhibits the proliferation of multiple cell lines derived from various cancer tissues, including HCT116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1, and Raji cells with EC50 of 23 nM, 21 nM, 11 nM, 15 nM, 32 nM, 36 nM, and 37 nM, respectively. This compound treatment (100 nM) in NCI-H460 cells induces an accumulation of mitotic cells with monopolar spindles and positive staining for histone H3 phosphoserine 10, confirming that cells are arrested early in the M phase, followed by induction of apoptosis. [1] Low nanomolar concentrations of this inhibitor display potent inhibitory activity against neuroblastoma (NB) tumor-initiating cells (NB TIC) with EC50 of 21 nM, whereas only micromolar concentrations of it are cytotoxic for normal pediatric neural stem cells. [2] It induces growth arrest of Daoy and ONS-76 medulloblastoma cells similar to BI 2536. [3]
in vivo

Administration of BI6727 significantly inhibits the growth of multiple human carcinoma xenografts including HCT116, NCI-H460, and taxane-resistant CXB1 colon carcinoma, accompanied by an increase in the mitotic index as well as an increase in apoptosis. [1] In in vivo studies, this compound shows better toxicity and pharmacokinetic profile compared to BI2536. [3]
特徴 A high volume of distribution, indicating good tissue penetration, and a long terminal half-life.

プロトコル(参考用のみ)

キナーゼアッセイ In vitro kinase assays
Recombinant human Plk1 (residues 1-603) is expressed as NH2-terminal, GST-tagged fusion protein using a baculoviral expression system and purified by affinity chromatography using glutathione-agarose. Enzyme activity assays for Plk1 are done in the presence of serially diluted this compound using 20 ng of recombinant kinase and 10 μg casein from bovine milk as substrate. Kinase reactions are done in a final volume of 60 μL for 45 minutes at 30 °C [15 mM MgCl2, 25 mM MOPS (pH 7.0), 1 mM DTT, 1% DMSO, 7.5 μM ATP, 0.3 μCi γ-32P-ATP]. Reactions are terminated by the addition of 125 μL of ice-cold 5% TCA. After transferring the precipitates to MultiScreen mixed ester cellulose filter plates, plates are washed with 1% TCA and quantified radiometrically. Dose-response curves are used for calculating IC50 value.
細胞アッセイ 細胞株 HCT116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1, and Raji
濃度 Dissolved in DMSO, final concentrations ~1 μM
反応時間 24, 48, and 72 hours
実験の流れ

Cell proliferation assays are done by incubating cells in the presence of various concentrations of this compound for 24, 48, and 72 hours and cell growth is assessed by measuring Alamar blue dye conversion in a fluorescence spectrophotometer. Effective concentrations at which cellular growth is inhibited by 50% (EC50) are extrapolated from the dose-response curve fit. To determine the DNA content, cell suspensions are fixed in 80% ethanol, treated for 5 minutes with 0.25% Triton X-100 in PBS, and incubated with 0.1% RNase and 10 μg/mL propidium iodide in PBS for 20 minutes at room temperature. Cell cycle profiles are determined by flow cytometric analysis.
動物実験 動物モデル Female BomTac:NMRI-Foxn1nu mice grafted s.c. with HCT116, NCI-H460, or CXB1 cells
投薬量 ~25 mg/kg/day
投与方法 Injected i.v., or given intragastrally via gavage needle

参考

  • https://pubmed.ncbi.nlm.nih.gov/19383823/
  • https://pubmed.ncbi.nlm.nih.gov/21303981/
  • https://pubmed.ncbi.nlm.nih.gov/22390279/

カスタマーフィードバック

Data from [Oncogene, 2013, 10.1038/onc.2013.518]

Data independently produced by , , Dr. Xiangbing Meng from University of Iowa

, , Dr. Xiangbing Meng from University of Iowa

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Unraveling the impact of crizotinib to promote megakaryopoiesis for alleviating thrombocytopenia in myelodysplastic neoplasms [ Leukemia, 2025, 10.1038/s41375-025-02729-w] PubMed: 40813622
TUFT1 regulates cancer progression by suppressing centrosome amplification and mitotic spindle multipolarity [ Cell Death Dis, 2025, 16(1):673] PubMed: 41022752
Deep transfer learning approach for automated cell death classification reveals novel ferroptosis-inducing agents in subsets of B-ALL [ Cell Death Dis, 2025, 16(1):396] PubMed: 40382332
PLK1 blockade enhances the anti-tumor effect of MAPK inhibition in pancreatic ductal adenocarcinoma [ Cell Rep, 2025, 44(4):115541] PubMed: 40188436
Cyclin E1 overexpression sensitizes ovarian cancer cells to WEE1 and PLK1 inhibition [ Oncogene, 2025, 10.1038/s41388-025-03312-4] PubMed: 39994376
PLK1 Inhibition Induces Synthetic Lethality in Fanconi Anemia Pathway-Deficient Acute Myeloid Leukemia [ Cancer Res Commun, 2025, 5(4):648-667] PubMed: 40111122
Systematic analysis of RNA-binding proteins identifies targetable therapeutic vulnerabilities in osteosarcoma [ Nat Commun, 2024, 15(1):2810] PubMed: 38561347
Mechanism of co-operation of mutant IL-7Rα and mutant NRAS in acute lymphoblastic leukemia: role of MYC [ Haematologica, 2024, 109(6):1726-1740] PubMed: 38031763
Proteomic analysis reveals a PLK1-dependent G2/M degradation program and a role for AKAP2 in coordinating the mitotic cytoskeleton [ Cell Rep, 2024, 43(8):114510] PubMed: 39018246
PLK1 and FoxM1 expressions positively correlate in papillary thyroid carcinoma and their combined inhibition results in synergistic anti-tumor effects [ Mol Oncol, 2024, 10.1002/1878-0261.13610] PubMed: 38361222

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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