Volasertib

Catalog No.S2235 Batch:S223510

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Technical Data

Formula

C34H50N8O3
Molecular Weight 618.81 CAS No. 755038-65-4
Solubility (25°C)* In vitro DMSO 20 mg/mL (32.32 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Add solvents to the product individually and in order)
Clear solution
5%DMSO 40%PEG300 5%Tween80 50%ddH2O
1.15mg/ml Taking the 1 mL working solution as an example, add 50 μL of 23 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
Clear solution
4%DMSO Corn oil
2.0mg/ml Taking the 1 mL working solution as an example, add 40 μL of 50 mg/ml clear DMSO stock solution to 960 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results. 
* <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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description 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.
Targets
PLK1 [1]
(Cell-free assay)
0.87 nM
In vitro Like BI2536, BI6727 is an ATP-competitive kinase inhibitor from the dihydropteridinone class of compounds. In addition to Plk1, BI6727 also potently inhibits two closely related kinases Plk2 and Plk3 with IC50 of 5 nM and 56 nM, respectively. BI6727 at concentrations up to 10 μM displays no inhibitory activity against a panel of >50 other kinases. BI6727 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. BI6727 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 BI6727 display potent inhibitory activity against neuroblastoma (NB) tumor-initiating cells (NB TIC) with EC50 of 21 nM, whereas only micromolar concentrations of BI6727 are cytotoxic for normal pediatric neural stem cells. [2] BI6727 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, BI6727 shows better toxicity and pharmacokinetic profile compared to BI2536. [3]
Features A high volume of distribution, indicating good tissue penetration, and a long terminal half-life.

Protocol (from reference)

Kinase Assay:[1]
  • 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 BI6727 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.
Cell Assay:[1]
  • Cell lines

    HCT116, NCI-H460, BRO, GRANTA-519, HL-60, THP-1, and Raji

  • Concentrations

    Dissolved in DMSO, final concentrations ~1 μM

  • Incubation Time

    24, 48, and 72 hours

  • Method

    Cell proliferation assays are done by incubating cells in the presence of various concentrations of BI6727 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.
Animal Study:[1]
  • Animal Models

    Female BomTac:NMRI-Foxn1nu mice grafted s.c. with HCT116, NCI-H460, or CXB1 cells

  • Dosages

    ~25 mg/kg/day

  • Administration

    Injected i.v., or given intragastrally via gavage needle

Customer Product Validation

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

, , Dr. Xiangbing Meng from University of Iowa

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

Data from [Data independently produced by , , Clin Cancer Res, 2018, 24(18):4588-4601]

Selleck's Volasertib has been cited by 175 publications

Systematic analysis of RNA-binding proteins identifies targetable therapeutic vulnerabilities in osteosarcoma [ Nat Commun, 2024, 15(1):2810] PubMed: 38561347
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
PLK1 phosphorylates RhoGDI1 and promotes cancer cell migration and invasion [ Cancer Cell Int, 2024, 24(1):73] PubMed: 38355643
Eph signal inhibition potentiates the growth-inhibitory effects of PLK1 inhibition toward cancer cells [ Eur J Pharmacol, 2024, 963:176229] PubMed: 38072041
Multidimensional screening of pancreatic cancer spheroids reveals vulnerabilities in mitotic and cell-matrix adhesion signaling that associate with metastatic progression and decreased patient survival [ Biochem Biophys Res Commun, 2024, 703:149575] PubMed: 38382357
Polθ is phosphorylated by PLK1 to repair double-strand breaks in mitosis [ Nature, 2023, 621(7978):415-422] PubMed: 37674080
Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry [ Nat Commun, 2023, 14(1):355] PubMed: 36683055
Molecular landscape and functional characterization of centrosome amplification in ovarian cancer [ Nat Commun, 2023, 14(1):6505] PubMed: 37845213
Multiplexed kinase interactome profiling quantifies cellular network activity and plasticity [ Mol Cell, 2023, 83(5):803-818.e8] PubMed: 36736316
PLK1 inhibition dampens NLRP3 inflammasome-elicited response in inflammatory disease models [ J Clin Invest, 2023, 133(21)e162129] PubMed: 37698938

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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